Our previous study demonstrated that combined transplantation of bone marrow mesenchymal stem cells and retinal progenitor cells in rats has therapeutic effects on retinal degeneration that are superior to transplanta...Our previous study demonstrated that combined transplantation of bone marrow mesenchymal stem cells and retinal progenitor cells in rats has therapeutic effects on retinal degeneration that are superior to transplantation of retinal progenitor cells alone.Bone marrow mesenchymal stem cells regulate and interact with various cells in the retinal microenvironment by secreting neurotrophic factors and extracellular vesicles.Small extracellular vesicles derived from bone marrow mesenchymal stem cells,which offer low immunogenicity,minimal tumorigenic risk,and ease of transportation,have been utilized in the treatment of various neurological diseases.These vesicles exhibit various activities,including anti-inflammatory actions,promotion of tissue repair,and immune regulation.Therefore,novel strategies using human retinal progenitor cells combined with bone marrow mesenchymal stem cell-derived small extracellular vesicles may represent an innovation in stem cell therapy for retinal degeneration.In this study,we developed such an approach utilizing retinal progenitor cells combined with bone marrow mesenchymal stem cell-derived small extracellular vesicles to treat retinal degeneration in Royal College of Surgeons rats,a genetic model of retinal degeneration.Our findings revealed that the combination of bone marrow mesenchymal stem cell-derived small extracellular vesicles and retinal progenitor cells significantly improved visual function in these rats.The addition of bone marrow mesenchymal stem cell-derived small extracellular vesicles as adjuvants to stem cell transplantation with retinal progenitor cells enhanced the survival,migration,and differentiation of the exogenous retinal progenitor cells.Concurrently,these small extracellular vesicles inhibited the activation of regional microglia,promoted the migration of transplanted retinal progenitor cells to the inner nuclear layer of the retina,and facilitated their differentiation into photoreceptors and bipolar cells.These findings suggest that bone marrow mesenchymal stem cell-derived small extracellular vesicles potentiate the therapeutic efficacy of retinal progenitor cells in retinal degeneration by promoting their survival and differentiation.展开更多
Background:Zucker diabetic fatty(ZDF)rats exhibit significant phenotypic variability despite genetic uniformity,yet a comprehensive characterization of these divergent phenotypes remains limited.Methods:Male ZDF(fa/fa...Background:Zucker diabetic fatty(ZDF)rats exhibit significant phenotypic variability despite genetic uniformity,yet a comprehensive characterization of these divergent phenotypes remains limited.Methods:Male ZDF(fa/fa)rats(4 months,n=22)and ZDF(fa/+)lean controls(n=10)were maintained on standard chow for 6 months.Based on metabolic trajectory,ZDF(fa/fa)rats were stratified into three phenotypes:obese normoglycemic(O,n=8),dia-betic with cachexia(D,n=8),and diabetic without cachexia(D-C,n=6).Comprehensive assessments included body weight,glycemic control,hepatic function,oxidative stress markers,and inflammatory cytokines.Results:Principal coordinate analysis confirmed significant metabolic separation between phenotypes(p25 mmol/L),insulin depletion,elevated hepatic enzymes(alanine ami-notransferase[ALT]increased 2.5-fold,p<0.01),elevated interleukin-6,and delayed pain response.Diabetic rats without cachexia(D-C)exhibited intermediate hypergly-cemia(≈13 mmol/L,p<0.001 vs.control)with preserved insulin levels,and elevated fibroblast growth factor 21(FGF21)and soluble receptor for advanced glycation end products(sRAGE).Obese normoglycemic(O)rats maintained normoglycemia with hy-perinsulinemia and elevated triglycerides.Conclusion:Under identical genetic and environmental conditions,ZDF(fa/fa)rats de-velop distinct metabolic phenotypes encompassing euglycemic obesity,pre-cachectic diabetes,and advanced cachectic diabetes.Phenotypic stratification is essential for accurate interpretation of ZDF experimental data and underscores the importance of characterizing individual metabolic trajectories when diabetic complications and therapeutic interventions are assessed in this model.展开更多
Central pattern generators(CPGs)are neural circuits which are found in both invertebrates and vertebrates,and are capable of generating rhythmic patterns of neural activity without receiving any rhythmic input.The mec...Central pattern generators(CPGs)are neural circuits which are found in both invertebrates and vertebrates,and are capable of generating rhythmic patterns of neural activity without receiving any rhythmic input.The mechanism by which CPG controls alternating and turning movements in vertebrates has not yet been fully understood.In this paper,a new CPG model for rat hindlimbs is proposed to unravel the above mechanism based on recent physiological experimental results.The model is obtained by adding commissural interneurons(CINs,including V0,V3,and CINi populations)and chx10 Gi neurons into Deng’s CPG model.Based on our proposed CPG model,different alternating gaits in the rat hindlimb model can be achieved by ablating different populations of commissural interneurons,which is consistent with physiological experimental findings.Then,turning movements are studied by applying unilateral excitatory and inhibitory stimuli to chx10 Gi neurons which are connected to the flexion side of the CPG with inhibitory synapses.It is found that unilateral activation leads to turning towards the same side,while unilateral inhibition results in turning towards the opposite side,which is also consistent with the results in physiological experiments.Finally,the ion-channel control mechanism of CPG burst rhythms is investigated,and it is found that the CPG burst rhythm is most sensitive to sodium ion channels,with a significantly greater impact than the influence of reciprocal inhibition on the rhythm.The proposed CPG model provides a new perspective for understanding motor neural mechanism of vertebrates,and also could be adopted in motion control of hindlimb robots.展开更多
This study aims to establish a theoretical foundation for selecting and constructing animal models in clinical research on spine-related diseases.By establishing surgical models in three experimental animal species—m...This study aims to establish a theoretical foundation for selecting and constructing animal models in clinical research on spine-related diseases.By establishing surgical models in three experimental animal species—mice,rats,and rabbits—we compare their respective advantages and disadvantages.First,three experimental animals of each of the three species were selected in good health.Subsequently,the experimental animals were dissected and several indices of the designated intervertebral discs and the height of the adjacent vertebrae were measured.At the same time,the ease of the surgical operation was assessed intraoperatively(in terms of the ease of preoperative localization,the clarity of the intraoperative structures,and the length of the surgical operation).In addition,the animal type most suitable for the construction of a spinal fusion surgery model was evaluated.Finally,a rabbit spinal fusion surgical model was constructed and evaluated by palpation and gross view of the tissue to assess the degree of spinal fusion.The data on the disc structure of rabbits have more advantages than those of mice and rats in constructing surgical models,with easier preoperative localization,more precise intraoperative structure,and shorter surgery time.Spinal fusion surgery in rabbits was successful,with a significant trend toward fusion at 4 weeks postoperatively.Rabbits were superior to mice and rats as experimental animals for establishing spinal fusion surgery models,and the fusion models were effective.展开更多
Objective:To investigate the sterilizing potential of zinc gluconate,calcium chloride(CaCl2)and cadmium chloride(CdCl2)following a single intratesticular administration in adult male rats.Methods:60 adult male W...Objective:To investigate the sterilizing potential of zinc gluconate,calcium chloride(CaCl2)and cadmium chloride(CdCl2)following a single intratesticular administration in adult male rats.Methods:60 adult male Wistar albino rats(Rattus norvegicus)weighing 160-200 g and aged 5-6 months randomly received a single intratesticular injection of normal saline(Group A),zinc gluconate 13.3 mg/mL plus L-Arginine(Group B),20%CaCl2(Group C),and CdCl20.5 mg/kg body weight plus ethylenediaminetetraacetic acid(EDTA)(Group D),respectively,along the entire route from the caudoventral aspect of each testis.They were euthanized up to 180 days to evaluate reproductive tract toxicology.Results:The reproductive organ weights were markedly reduced,with testes severely atrophied in group B,pea-sized and stony hard in group C,and moderately reduced in group D.Azoospermia was evident in groups B and C,while sperm concentration was reduced to<1 million/mL with zero sperm motility in group D.Rats of groups B and C failed to show mounting and copulatory behaviour.A completely disorganized mesh of cellular elements was observed in the seminiferous tubules of group B,while pyknotic germ cell and arrest of spermatogenesis,exfoliated germ cells,occasional syncytial bodies and smaller Leydig cells were evident in groups C and D.Significantly reduced testosterone levels,increased luteinizing hormone(LH)and follicle-stimulating hormone(FSH)levels,returned to normal after 90 days in group D.Conclusions:Zinc gluconate and CaCl2injections severely affected the reproductive organs and libido and rats treated with CdCl2exhibited diminished spermatogenesis with normal libido.Thus,the need-based selection of intratesticular agents should consider their distinct effects on spermatogenesis,libido,and hormonal balance for achieving targeted sterilization outcomes.展开更多
Background:Mitochondrial DNA(mtDNA)mutations are implicated in a wide range of diseases,underscoring the need to elucidate the relationship between mtDNA mutations and disease pathology.These diseases are often charac...Background:Mitochondrial DNA(mtDNA)mutations are implicated in a wide range of diseases,underscoring the need to elucidate the relationship between mtDNA mutations and disease pathology.These diseases are often characterized by the presence of multiple mutations;however,research has been hampered by the lack of suitable animal models carrying multiplex mtDNA mutations.Such models cannot be produced through traditional breeding due to matrilineal inheritance of mtDNA.Methods:Based on the TALE-based mitochondrial genome editing tools,we generated rats harboring multiple mtDNA mutations by microinjecting mixed pairs of DdCBE plasmids into one-cell-stage zygotes.The efficiency of mtDNA editing and the potential off-target effects were assessed through deep sequencing and long reads sequencing methodologies.Results:In this study,we established double-and triple-site mutant rats with the editing efficiencies of up to 58.5%and confirmed that these mutations can be stably transmitted through the germline.Moreover,our results demonstrated that DdCBE-mediated mtDNA multi-site editing of mtDNA exhibits minimal off-target effects in both the mitochondrial and nuclear genomes in vivo.Conclusion:This work represents the first successful generation of heritable multi-site mtDNA mutant rats,providing a valuable model for elucidating the pathophysiological mechanisms of mitochondrial disorders and for developing potential therapeutics.展开更多
Vine tea is documented in ancient Chinese books as having the function of promoting blood circulation.However,its effects and mechanisms remain unclear.The aim of this study was to comprehensively investigate the prot...Vine tea is documented in ancient Chinese books as having the function of promoting blood circulation.However,its effects and mechanisms remain unclear.The aim of this study was to comprehensively investigate the protective potential and mechanisms of vine tea in high-fat diet rat through a combination of in vivo and in vitro experiments.The efficacy of vine tea was evaluated using a high-fat diet rat model and an oxidized low-density lipoprotein-treated cell model,with physiological and biochemical indicators measured in rat serum and cell supernatants.Transcriptomics was utilized to investigate alterations mRNA expression following the administration of dihydromyricetin in cell model.Metabolomics and 16S rRNA sequencing was employed to examine changes in metabolites in the serum and changes in gut microbiota of high-fat diet rats after administering vine tea extract.Vine tea extract and dihydromyricetin can reduce elevated levels of lipids,including total cholesterol and triglycerides,following modeling.Transcriptomic data indicate that dihydromyricetin exerts its effects by regulating ferroptosis signaling pathways.Metabolomic analysis demonstrates that the administration of vine tea extract influences the vitamin K cycle and glutathione,thereby alleviating the progression of ferroptosis.Additionally,16S rRNA sequencing reveals that vine tea extract increases Lactobacillaceae in the gut microbiota,which subsequently affects the levels of lysophosphatidylcholine,a major phospholipid component of oxidized low-density lipoprotein in serum.Our results indicate that vine tea can regulate ferroptosis signaling pathways and increase Lactobacillaceae in the gut microbiota,thereby exhibiting cardiovascular protective effects in high-fat diet rats.展开更多
Uncovering the underlying process of epileptogenesis is crucial for developing effective treatment strategies for epilepsy.However,the cellular and molecular changes throughout epileptogenesis are not fully understood...Uncovering the underlying process of epileptogenesis is crucial for developing effective treatment strategies for epilepsy.However,the cellular and molecular changes throughout epileptogenesis are not fully understood.In this study,single-nucleus RNA sequencing was performed on the hippocampus,temporal cortex,and thalamus across the acute,latent,and chronic phases in a pilocarpine-induced rat model and controls.We created a comprehensive single-nucleus transcriptomic atlas of rat epileptogenesis,consisting of 311,177 single nuclei.Our analysis revealed distinct transcriptional signatures across the three phases and regions,including significant gene expression changes in the acute phase and critical synaptic and neural network remodeling in the thalamus during the latent phase.Notably,we identified two novel astrocyte clusters during epileptogenesis,with the EX-Astro C3-IN pathway emerging as a potential intervention target.The dataset provides a detailed understanding of the dynamic cellular and molecular landscape of epileptogenesis.展开更多
Phrenic nerve stimulation(PNS)may preserve diaphragm activation and mitigate multiorgan injury during mechanical ventilation(MV);however,a minimal invasive rat model integrating PNS with MV is lacking.We established a...Phrenic nerve stimulation(PNS)may preserve diaphragm activation and mitigate multiorgan injury during mechanical ventilation(MV);however,a minimal invasive rat model integrating PNS with MV is lacking.We established an omohyoid muscle-based PNS rat model combined with MV.Bilateral nerves were exposed within 20±2 min by transection at the intermediate tendon of omohyoid muscle,minimizing trauma and bleeding.Threshold stimulation(0.6±0.2 mA)correlated with body weight.Ventilator-synchronized stimulation increased compound muscle action potentials by~30%,whereas histology confirmed intact nerve.Physiological parameters remained stable throughout ventilation.This model provides a safe and scalable platform for mechanistic and preclinical studies on PNS-mediated protection against MV-induced organ injury.展开更多
[Objectives]To investigate the mechanism by which Dachaihu Decoction affects visceral pain behavior in a rat model of ulcerative colitis(UC).[Methods]Twenty-one male Sprague-Dawley(SD)rats were randomly and equally di...[Objectives]To investigate the mechanism by which Dachaihu Decoction affects visceral pain behavior in a rat model of ulcerative colitis(UC).[Methods]Twenty-one male Sprague-Dawley(SD)rats were randomly and equally divided into a control group,a UC group,and a Dachaihu Decoction group(n=7 per group).After treatment completion,visceral pain behavior and colonic motility indices were assessed using in vivo colorectal distension(CRD)and abdominal withdrawal reflex(AWR)tests.[Results]Compared to the UC group,the Dachaihu Decoction group exhibited increased colon length,elevated colonic basal tension,heightened peak contractile tension,and increased contraction frequency.These differences were statistically significant(P<0.05).[Conclusions]Dachaihu Decoction may ameliorate visceral hyperalgesia induced by rectal distension stimuli in the UC rat model by improving colonic motility.展开更多
Objective:To establish a liquid chromatography tandem mass spectrometry(HPLC-MS/MS)method to determine amygdalin and paeoniflorin in rat blood serum.Method:After protein precipitation by acetonitrile,a gradient elutio...Objective:To establish a liquid chromatography tandem mass spectrometry(HPLC-MS/MS)method to determine amygdalin and paeoniflorin in rat blood serum.Method:After protein precipitation by acetonitrile,a gradient elution procedure was performed to separate the samples by using acetonitrile and ammonium acetate buffer as the mobile phase.The quantitative determination was based on an HPLC-MS/MS in negative electron spray ionization mode and in multiple reaction monitoring(MRM)mode.The precursor to product ion transitions for amygdalin and paeoniflorin were 456.2 to 323.1 and 479.2 to 121.0,respectively.Results:The linear ranges of amygdalin and paeoniflorin were 1-300 ng/mL(rAmy=0.9994,rPae=0.9993)with the lowest limits of quantification were 0.3 ng/ml.The extract recovery of amygdalin and paeoniflorin were 91.1%,94.2%,92.0%and 90.3%,93.7%,94.1%at concentrations of 3,20,100 ng/mL,respectively.All the intra and inter day precisions of analysis were less than 15%,and the RE were in the range of±15%.Conclusion:The method is specific,sensitive,accurate,and suitable for determination of amygdalin and paeoniflorin in rat blood serum.展开更多
Stroke induces profound neuroinflammation and systemic immune dysregulation,including disturbances in gut homeostasis.Experimental evidence suggests that intestinal barrier permeability(IBP)and bacterial translocation...Stroke induces profound neuroinflammation and systemic immune dysregulation,including disturbances in gut homeostasis.Experimental evidence suggests that intestinal barrier permeability(IBP)and bacterial translocation(BT)critically influence stroke outcomes.However,biological variability among commonly used rodent substrains has received limited attention.In this pilot study,we compared poststroke immune responses in two Wistar rat substrains obtained from different suppliers:RccHan(Envigo)and RjHan(Janvier).Naive animals(n=4)and rats subjected to permanent cerebral ischemia(n=8 per substrain)were evaluated 72 h after middle cerebral artery occlusion and stratified according to the presence or absence of BT.Immune cell populations in blood and bone marrow were analyzed using flow cytometry,and leukocyte infiltration into ischemic brain tissue was quantified using immunohisto-chemistry.Differences were considered statistically significant when p<0.05.Both substrains developed significant infarcts and neurological deficits.RccHan rats exhibited larger infarct volumes and more extensive BT across multiple organs.In contrast,RjHan rats exhibited BT mainly confined to mesenteric lymph nodes but exhibited greater IBP.Although dissemination was broader in RccHan rats,overall bacterial burden was slightly lower compared with RjHan,and extraintestinal bacterial composition differed between groups.Particularly,RjHan rats exhibited stronger systemic and central immune activation,with significant alterations in lymphocyte and monocyte populations and enhanced granulocyte and T-cell infiltration within ischemic lesions.These findings demonstrate that substrain origin profoundly influences poststroke intestinal barrier integrity,bacterial dissemination,and immune responses considering substrain-related variability is essential to improve reproducibility and translational relevance in preclinical stroke research.展开更多
AIM:To examine the ocular toxicity linked to sildenafilusage and the possible protective benefits of adenosinetriphosphate(ATP)against this toxicity in rats.METHODS:Twenty-four male albino Wistar-type ratswere divided...AIM:To examine the ocular toxicity linked to sildenafilusage and the possible protective benefits of adenosinetriphosphate(ATP)against this toxicity in rats.METHODS:Twenty-four male albino Wistar-type ratswere divided into four equal groups(n=6/group)as follows:healthy group(HG),ATP-only group(ATPG),sildenafil-onlygroup(SILG),and ATP+sildenafil group(ATP+SLD).ATPG andATP+SLD groups were injected intraperitoneally with ATP(4 mg/kg),while SILG and HG groups were injected withsaline(0.9%NaCl)by the same route as a solvent.One hourafter the administration of ATP and solvent,sildenafil(10 m g/k g)was administered orally to the SILG andATP+SLD groups.This procedure was repeated once a dayfor 4wk.The animals were then sacrificed,eyeballs wereremoved and oxidant and antioxidant parameters weremeasured biochemically.Additionally,the ocular tissueswere evaluated histopathologically.RESULTS:Sildenafil increased oxidant(malondialdehyde)levels and decreased antioxidant levels(total glutathione,superoxide dismutase,catalase)in rat ocular tissues andcaused severe oxidative stress.In addition,sildenafil hasbeen shown histopathologically to cause oxidative damagein retinal layers.ATP treatment suppressed oxidative stressand attenuated histopathological damage in the retinal layers.CONCLUSION:ATP protects retinal tissue againstsildenafil-induced ocular oxidative damage in rats andmay contribute to the development of novel approaches toprevent or treat this damage.展开更多
The simultaneous characterization of histological alterations and distinct celldeath pathways associated with diabetic cardiomyopathy(DCM)has not beencomprehensively explored and may differ depending on the experiment...The simultaneous characterization of histological alterations and distinct celldeath pathways associated with diabetic cardiomyopathy(DCM)has not beencomprehensively explored and may differ depending on the experimental model.Weevaluated cardiac histological changes and markers of apoptosis,cell death associatedwith mitochondrial permeability transition pore(mPTP)opening(necrosis),andautophagy in early and advanced stages of streptozotocin(STZ)-induced diabetesin rats receiving insulin daily to prevent mortality while maintaining hyperglycemia.Adult male Sprague–Dawley rats(n=4–5)were randomly assigned to receive STZ(diabetic group)or saline(mock)and followed up for 4 or 12 weeks.Hearts wereprocessed for histological examination and immunohistochemical detection of activecaspase-3,beclin-1,and cyclophilin D.STZ significantly increased glycemia at bothtime points,whereas body weight reduction was observed only at 12 weeks.Noevidence of cardiac hypertrophy,fibrosis,or structural injury was detected in diabeticrats at either stage.Expression of caspase-3,beclin-1,and cyclophilin D decreased at12 weeks compared with 4 weeks,regardless of treatment;however,cyclophilin D waselevated in diabetic hearts at 4 weeks.These results suggest an early susceptibilityto mPTP opening under persistent hyperglycemia,despite the absence of overthistological damage.They also underscore the critical importance of insulin dosingand study duration when interpreting data from STZ-based models.Further studiesare warranted to determine how even minimal insulin administration may shape thetemporal dynamics of cell death during the progression of DCM.展开更多
Background:Atherosclerosis begins with dyslipidemia,vascular inflammation,and en-dothelial dysfunction.Rodent models that capture these early events are needed for mechanistic and interventional studies.This study eva...Background:Atherosclerosis begins with dyslipidemia,vascular inflammation,and en-dothelial dysfunction.Rodent models that capture these early events are needed for mechanistic and interventional studies.This study evaluated whether a cholesterol-rich,high-fat diet(HFD)supplemented with vitamin D and propylthiouracil(PTU)promotes a pro-atherogenic phenotype in rats,as evidenced by dyslipidemia,inflam-mation,markers of endothelial dysfunction,and early vascular remodeling.Methods:Male Sprague-Dawley rats(n=18)received standard chow or a HFD con-taining 2%cholesterol,3%lard,0.5%cholate,vitamin D(200000 IU/kg),and PTU(0.2%w/w)for 11 weeks.Terminal serum total cholesterol,high-density lipoprotein,low-density lipoprotein(LDL)/very low-density lipoprotein(VLDL),triglycerides,calcium,interleukin-6(IL-6),C-reactive protein,serum amyloid A(SAA),circulating endothelial nitric oxide synthase(eNOS),and intracellular adhesion molecule-1(ICAM-1)were measured.The aorta,the coronary arteries,and the liver were examined histologically.Results:HFD-fed rats developed significant hypercholesterolemia with higher total cholesterol and LDL/VLDL(p<0.0001)and lower triglycerides(p<0.0001)versus controls.Serum calcium was higher(p<0.0001)without vascular calcification.Aortae exhibited wall thickening,smooth-muscle disarray,mononuclear infiltrates,and focal foam cell-like changes;coronary arteries exhibited endothelial irregularities and perivascular infiltrates.Livers exhibited micro-and macrovesicular steatosis.IL-6 and SAA were higher(p<0.05),and circulating eNOS was lower(p<0.05);ICAM-1 did not differ significantly.Conclusion:An 11-week vitamin D/PTU-supplemented HFD induces an LDL-dominant dyslipidemia with systemic inflammation and evidence consistent with endothelial dysfunction,alongside histological features of early vascular remodeling and hepatic steatosis.This nongenetic model may be useful for studying early atherogenic changes.展开更多
BACKGROUND Chronic radiation proctitis(CRP),a major complication of pelvic radiotherapy,lacks effective treatments and a standardized animal model that recapitulates its late fibrotic and angiogenic pathologies.AIM To...BACKGROUND Chronic radiation proctitis(CRP),a major complication of pelvic radiotherapy,lacks effective treatments and a standardized animal model that recapitulates its late fibrotic and angiogenic pathologies.AIM To establish a model that recapitulates the features of human CRP and to investigate the mechanisms of irreversible tissue damage.Rats were randomized into a control group and single-dose irradiation groups(12.5-37.5 Gy).Rectal injury was assessed via 6-month continuous endoscopic observation,the modified Vienna Rectoscopy Score,and histological analysis.Additionally,rectal tissues were analyzed for cytoskeletal protein alterations.RESULTS Acute mucosal injury was reversible at doses below 20 Gy.In the 20-35 Gy groups,persistent radiation proctitis,marked telangiectasia,and severe mucosal fibrosis indicated irreversible injury.Furthermore,cytoskeletal proteins,particularly tubulin,decreased sharply at doses≥20 Gy.Vascular endothelial growth factor was mildly upregulated mainly in the deep tissue layers during the acute phase,whereas it was significantly increased in the mucosa of the highdose groups during the chronic phase.CONCLUSION Single-dose radiation(20-35 Gy)induces CRP.Reduced tubulin expression marks the early transition to chronic injury(P<0.0001).展开更多
AIM:To investigate the effects of zingerone(ZO)on the retina in diabetic rats.METHODS:A total of 70 rats were randomly selected and divided into seven groups[diabetic group(Dm+;n=10),diabetic+metformin group(Dm+Met;n=...AIM:To investigate the effects of zingerone(ZO)on the retina in diabetic rats.METHODS:A total of 70 rats were randomly selected and divided into seven groups[diabetic group(Dm+;n=10),diabetic+metformin group(Dm+Met;n=10),diabetic+ZO25 group(Dm+ZO25;n=10),diabetic+ZO50 group(Dm+ZO50;n=10),diabetic+metformin group+ZO 50 Group(Dm+Met+ZO50;n=10)].Diabetes was induced by streptozotocin(STZ),and metformin and two different doses of ZO were administered via gavage.Retinal tissues were evaluated by histopathological and immunohistochemical analyses.RESULTS:In diabetic rats,severe retinal inflammation,tissue necrosis,and increased tumor necrosis factor-α(TNF-α)expression were observed.ZO administration reduced these effects in a dose-dependent manner.Protective effects of metformin alone were limited,and no synergistic benefit was observed in ZO+Met groups.Administration of 50 mg/kg ZO to non-diabetic rats caused no retinal toxicity.Additionally,elevated 8-OHdG and c-Jun N-terminal kinase(JNK)expressions in diabetic retinopathy models were significantly reduced by ZO treatment.CONCLUSION:ZO can markedly reduce the pathological effects of the retina in a diabetic rat model.展开更多
BACKGROUND Spinal cord ischemia-reperfusion injury(IRI),which can occur as a result of temporary aortic occlusion during resection of thoracoabdominal aneurysms,can be an unpredictable and devastating complication of ...BACKGROUND Spinal cord ischemia-reperfusion injury(IRI),which can occur as a result of temporary aortic occlusion during resection of thoracoabdominal aneurysms,can be an unpredictable and devastating complication of aortic surgery.There are no specific medications or guidelines for the prevention and treatment of spinal cord IRI(SCIRI).It is now known that IRI not only exacerbates local tissue damage when blood flow is restored but also affects distant organs,such as the liver,lungs,and brain,through mediators released into the systemic circulation.Studies show that ozone pretreatment reduces oxidative damage by increasing antioxidant capacity,promotes anti-inflammatory signaling,improves blood circulation,and ameliorates IRI.Our study is one of the first to examine the effects of ozone on remote organs(liver,lung,and brain)when administered via different routes(intrathecal,intraperitoneal,rectal)in a spinal cord ischemia-reperfusion model.AIM To determine whether ozone administered by different routes offers multiorgan protection in SCIRI.METHODS Thirty adult Wistar albino rats were randomly divided into five groups(n=6,each):A control(C group),an IR group,an IR rectal ozone(IRRO)group,an IR intrathecal ozone(IRITO),and an IR intraperitoneal ozone(IRIPO).In the IR groups,the spinal cord IR models(a 30-minute ischemia period was applied to the infrarenal abdominal aorta using an atraumatic vascular clamp,and then a 120-minute reperfusion period was applied by removing the clamp)were applied.An ozone-oxygen mixture of 1 mg/kg(50μg/mL)was administered by rectal insufflation to the IRRO group,0.7 mg/kg(50μg/mL)via the peritoneum to the IRIPO group,and 20μL(20μg/mL)intrathecally to the IRITO group 30 minutes before midline laparotomy.At the end of the reperfusion procedure,histopathological and biochemical analyses of liver,lung,and brain tissues were performed.RESULTS Liver tissue malondialdehyde(MDA)levels were significantly lower,and catalase(CAT)enzyme activities were significantly higher in the IRRO,IRITO,and IRIPO groups than in the IR group.Histopathologically,we had favorable results from all three ozone applications compared to the IR group.Lung tissue MDA levels were significantly lower,and CAT enzyme activities were significantly higher in the IRITO and IRIPO groups than in the IR group.We had more positive results in the IRRO group than in the IR group,but the difference was not found to be significant.Histopathologically,we obtained significantly more positive results in the IRITO and IRIPO groups compared with the IR group regarding all the criteria we evaluated.Our results in the IRRO group were also positive.Brain tissue MDA levels were significantly lower and CAT enzyme activities significantly higher in the IRITO and IRIPO groups than in the IR group.We had positive results in the IRRO group compared with the IR group.Histopathologically,we obtained significantly more positive results in the IRITO group regarding all the criteria we evaluated.CONCLUSION We observed histopathologically that single-dose ozone pretreatment administered intrathecally,intraperitoneally,or rectally had positive effects on liver,lung,and brain tissues compared to the IR group in an SCIRI model in rats due to its antioxidant effect.The best histopathological results were obtained with intrathecal,intraperitoneal,and rectally administered ozone,in that order,in all three tissues.展开更多
BACKGROUND Diabetes is an endocrinopathy characterized by the inability to produce insulin or insufficient insulin production because of the destruction of beta cells in the pancreas caused by autoimmune or other epid...BACKGROUND Diabetes is an endocrinopathy characterized by the inability to produce insulin or insufficient insulin production because of the destruction of beta cells in the pancreas caused by autoimmune or other epidemiological factors.Diabetes can lead to physical and psychological complications.AIM To investigate early behavioral changes in an experimental diabetes model in juvenile rats.METHODS In this study,a total of 14 juvenile male Wistar rats(7 rats per group)were used.To induce the diabetes model,120 mg/kg streptozotocin(STZ)was administered,while the control group received 1 mL/kg physiological saline.The open field test and the hole-board test were performed for five minutes each.Unpaired comparisons were evaluated using Student’s t test or the Mann-Whitney U test.Correlations were analyzed using the Pearson test.RESULTS Severe hyperglycemia was observed in rats in the diabetes mellitus model induced by STZ,and all diabetic rats displayed glucose levels above 400 mg/dL.In the open-field test,the time spent in the central area,the number of rearings,and the total distance traveled were significantly lower in diabetic rats than in naive rats(P<0.05).In the hole-board test,the duration and frequency of total head dipping were considerably lower in diabetic rats than in healthy rats(P<0.01).The grooming time(P<0.01)and freezing time(P<0.0001)increased dramatically in the diabetes mellitus group.A remarkable correlation was found between behavioral changes and hyperglycemia.CONCLUSION Our data indicate that early-stage diabetes induced by STZ increases anxiety-like behaviors and impairs exploratory behaviors.These behavioral changes may also occur in children with undiagnosed or untreated hyperglycemia and can provide important clues in clinical practice.展开更多
[Objectives]To observe the effect of Shenfu Injection on regional cerebral blood flow(RCBF)in a rat model of acute cerebral infarction.[Methods]Thirty Sprague-Dawley(SD)rats were randomly assigned to three groups:cont...[Objectives]To observe the effect of Shenfu Injection on regional cerebral blood flow(RCBF)in a rat model of acute cerebral infarction.[Methods]Thirty Sprague-Dawley(SD)rats were randomly assigned to three groups:control group,model group,and Shenfu Injection group(administered via tail vein injection at 2 mL/100 g body weight).The model was established using the middle cerebral artery occlusion(MCAO)method,and electroencephalogram(EEG)spike amplitude and RCBF were measured at 0,30,and 60 min,as well as 1,3,and 6 d post-reperfusion.[Results]Compared with the model group,the Shenfu Injection group exhibited significantly increased RCBF on day 3 and 6(P<0.05)and significantly decreased EEG spike amplitude on day 1,3,and 6(P<0.05).[Conclusions]Shenfu Injection improves regional cerebral blood flow in rats with acute cerebral infarction,potentially through mechanisms involving suppression of abnormal electrical discharges and dilatation of microvessels.展开更多
基金supported by the National Natural Science Foundation of China,Nos.82271132(to YL),82101167(to BB)the Natural Science Foundation of Chongqing,Nos.CSTB2022NSCQ-MSX0020(to BB),cstc2019jcyj-msxmX0473(to FC).
摘要Our previous study demonstrated that combined transplantation of bone marrow mesenchymal stem cells and retinal progenitor cells in rats has therapeutic effects on retinal degeneration that are superior to transplantation of retinal progenitor cells alone.Bone marrow mesenchymal stem cells regulate and interact with various cells in the retinal microenvironment by secreting neurotrophic factors and extracellular vesicles.Small extracellular vesicles derived from bone marrow mesenchymal stem cells,which offer low immunogenicity,minimal tumorigenic risk,and ease of transportation,have been utilized in the treatment of various neurological diseases.These vesicles exhibit various activities,including anti-inflammatory actions,promotion of tissue repair,and immune regulation.Therefore,novel strategies using human retinal progenitor cells combined with bone marrow mesenchymal stem cell-derived small extracellular vesicles may represent an innovation in stem cell therapy for retinal degeneration.In this study,we developed such an approach utilizing retinal progenitor cells combined with bone marrow mesenchymal stem cell-derived small extracellular vesicles to treat retinal degeneration in Royal College of Surgeons rats,a genetic model of retinal degeneration.Our findings revealed that the combination of bone marrow mesenchymal stem cell-derived small extracellular vesicles and retinal progenitor cells significantly improved visual function in these rats.The addition of bone marrow mesenchymal stem cell-derived small extracellular vesicles as adjuvants to stem cell transplantation with retinal progenitor cells enhanced the survival,migration,and differentiation of the exogenous retinal progenitor cells.Concurrently,these small extracellular vesicles inhibited the activation of regional microglia,promoted the migration of transplanted retinal progenitor cells to the inner nuclear layer of the retina,and facilitated their differentiation into photoreceptors and bipolar cells.These findings suggest that bone marrow mesenchymal stem cell-derived small extracellular vesicles potentiate the therapeutic efficacy of retinal progenitor cells in retinal degeneration by promoting their survival and differentiation.
基金VEGA,Grant/Award Number:2/0087/22APVV,Grant/Award Number:20-0411Slovak Recovery and Resilience Plan,Grant/Award Number:09I05-03-V02-00048,。
摘要Background:Zucker diabetic fatty(ZDF)rats exhibit significant phenotypic variability despite genetic uniformity,yet a comprehensive characterization of these divergent phenotypes remains limited.Methods:Male ZDF(fa/fa)rats(4 months,n=22)and ZDF(fa/+)lean controls(n=10)were maintained on standard chow for 6 months.Based on metabolic trajectory,ZDF(fa/fa)rats were stratified into three phenotypes:obese normoglycemic(O,n=8),dia-betic with cachexia(D,n=8),and diabetic without cachexia(D-C,n=6).Comprehensive assessments included body weight,glycemic control,hepatic function,oxidative stress markers,and inflammatory cytokines.Results:Principal coordinate analysis confirmed significant metabolic separation between phenotypes(p25 mmol/L),insulin depletion,elevated hepatic enzymes(alanine ami-notransferase[ALT]increased 2.5-fold,p<0.01),elevated interleukin-6,and delayed pain response.Diabetic rats without cachexia(D-C)exhibited intermediate hypergly-cemia(≈13 mmol/L,p<0.001 vs.control)with preserved insulin levels,and elevated fibroblast growth factor 21(FGF21)and soluble receptor for advanced glycation end products(sRAGE).Obese normoglycemic(O)rats maintained normoglycemia with hy-perinsulinemia and elevated triglycerides.Conclusion:Under identical genetic and environmental conditions,ZDF(fa/fa)rats de-velop distinct metabolic phenotypes encompassing euglycemic obesity,pre-cachectic diabetes,and advanced cachectic diabetes.Phenotypic stratification is essential for accurate interpretation of ZDF experimental data and underscores the importance of characterizing individual metabolic trajectories when diabetic complications and therapeutic interventions are assessed in this model.
基金supported by the National Natural Science Foundation of China(Grants Nos.12332004 and 12272092).
摘要Central pattern generators(CPGs)are neural circuits which are found in both invertebrates and vertebrates,and are capable of generating rhythmic patterns of neural activity without receiving any rhythmic input.The mechanism by which CPG controls alternating and turning movements in vertebrates has not yet been fully understood.In this paper,a new CPG model for rat hindlimbs is proposed to unravel the above mechanism based on recent physiological experimental results.The model is obtained by adding commissural interneurons(CINs,including V0,V3,and CINi populations)and chx10 Gi neurons into Deng’s CPG model.Based on our proposed CPG model,different alternating gaits in the rat hindlimb model can be achieved by ablating different populations of commissural interneurons,which is consistent with physiological experimental findings.Then,turning movements are studied by applying unilateral excitatory and inhibitory stimuli to chx10 Gi neurons which are connected to the flexion side of the CPG with inhibitory synapses.It is found that unilateral activation leads to turning towards the same side,while unilateral inhibition results in turning towards the opposite side,which is also consistent with the results in physiological experiments.Finally,the ion-channel control mechanism of CPG burst rhythms is investigated,and it is found that the CPG burst rhythm is most sensitive to sodium ion channels,with a significantly greater impact than the influence of reciprocal inhibition on the rhythm.The proposed CPG model provides a new perspective for understanding motor neural mechanism of vertebrates,and also could be adopted in motion control of hindlimb robots.
摘要This study aims to establish a theoretical foundation for selecting and constructing animal models in clinical research on spine-related diseases.By establishing surgical models in three experimental animal species—mice,rats,and rabbits—we compare their respective advantages and disadvantages.First,three experimental animals of each of the three species were selected in good health.Subsequently,the experimental animals were dissected and several indices of the designated intervertebral discs and the height of the adjacent vertebrae were measured.At the same time,the ease of the surgical operation was assessed intraoperatively(in terms of the ease of preoperative localization,the clarity of the intraoperative structures,and the length of the surgical operation).In addition,the animal type most suitable for the construction of a spinal fusion surgery model was evaluated.Finally,a rabbit spinal fusion surgical model was constructed and evaluated by palpation and gross view of the tissue to assess the degree of spinal fusion.The data on the disc structure of rabbits have more advantages than those of mice and rats in constructing surgical models,with easier preoperative localization,more precise intraoperative structure,and shorter surgery time.Spinal fusion surgery in rabbits was successful,with a significant trend toward fusion at 4 weeks postoperatively.Rabbits were superior to mice and rats as experimental animals for establishing spinal fusion surgery models,and the fusion models were effective.
基金financially assisted to Timanshi Chansoriya of the fellowship grant of UGC-NFPwD,New Delhi sanctioned vide UGC F.No.01-01/2019-Sch dated 06.11.2020(Serial No.352 ID:NFPWD-2018-20-UTP-6522).
摘要Objective:To investigate the sterilizing potential of zinc gluconate,calcium chloride(CaCl2)and cadmium chloride(CdCl2)following a single intratesticular administration in adult male rats.Methods:60 adult male Wistar albino rats(Rattus norvegicus)weighing 160-200 g and aged 5-6 months randomly received a single intratesticular injection of normal saline(Group A),zinc gluconate 13.3 mg/mL plus L-Arginine(Group B),20%CaCl2(Group C),and CdCl20.5 mg/kg body weight plus ethylenediaminetetraacetic acid(EDTA)(Group D),respectively,along the entire route from the caudoventral aspect of each testis.They were euthanized up to 180 days to evaluate reproductive tract toxicology.Results:The reproductive organ weights were markedly reduced,with testes severely atrophied in group B,pea-sized and stony hard in group C,and moderately reduced in group D.Azoospermia was evident in groups B and C,while sperm concentration was reduced to<1 million/mL with zero sperm motility in group D.Rats of groups B and C failed to show mounting and copulatory behaviour.A completely disorganized mesh of cellular elements was observed in the seminiferous tubules of group B,while pyknotic germ cell and arrest of spermatogenesis,exfoliated germ cells,occasional syncytial bodies and smaller Leydig cells were evident in groups C and D.Significantly reduced testosterone levels,increased luteinizing hormone(LH)and follicle-stimulating hormone(FSH)levels,returned to normal after 90 days in group D.Conclusions:Zinc gluconate and CaCl2injections severely affected the reproductive organs and libido and rats treated with CdCl2exhibited diminished spermatogenesis with normal libido.Thus,the need-based selection of intratesticular agents should consider their distinct effects on spermatogenesis,libido,and hormonal balance for achieving targeted sterilization outcomes.
基金Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences,Grant/Award Number:2021-I2M-1-024,2022-I2M-1-020 and 2023-I2M-2-001The Non-profit Central Research Institute Fund of the Chinese Academy of Medical Sciences,Grant/Award Number:2023-PT180-01+3 种基金Haihe Laboratory of Cell Ecosystem Innovation Fund,Grant/Award Number:HH24KYZX0007Open Research Project in State Key Laboratory of Vascular Homeostasis and Remodeling(Peking University),Grant/Award Number:202411State Key Laboratory Special Fund,Grant/Award Number:2060204National Key R&D Program of China,Grant/Award Number:2022YFF0710702。
摘要Background:Mitochondrial DNA(mtDNA)mutations are implicated in a wide range of diseases,underscoring the need to elucidate the relationship between mtDNA mutations and disease pathology.These diseases are often characterized by the presence of multiple mutations;however,research has been hampered by the lack of suitable animal models carrying multiplex mtDNA mutations.Such models cannot be produced through traditional breeding due to matrilineal inheritance of mtDNA.Methods:Based on the TALE-based mitochondrial genome editing tools,we generated rats harboring multiple mtDNA mutations by microinjecting mixed pairs of DdCBE plasmids into one-cell-stage zygotes.The efficiency of mtDNA editing and the potential off-target effects were assessed through deep sequencing and long reads sequencing methodologies.Results:In this study,we established double-and triple-site mutant rats with the editing efficiencies of up to 58.5%and confirmed that these mutations can be stably transmitted through the germline.Moreover,our results demonstrated that DdCBE-mediated mtDNA multi-site editing of mtDNA exhibits minimal off-target effects in both the mitochondrial and nuclear genomes in vivo.Conclusion:This work represents the first successful generation of heritable multi-site mtDNA mutant rats,providing a valuable model for elucidating the pathophysiological mechanisms of mitochondrial disorders and for developing potential therapeutics.
基金supported by Project of Zhangjiajie City’s Industry-Academia-Research Collaborative Innovation‘Open Project Leader’,Zhangjiajie City’s Project of Taking on Challenging Tasks by Responding to Calls for Solutions(JB20230530)Basic Research Funds Project for Central Universities of China(2023XCZX001,2020kfyXJJS120)Academician and Expert Workstations in Yunnan Province(202205AF150090).
摘要Vine tea is documented in ancient Chinese books as having the function of promoting blood circulation.However,its effects and mechanisms remain unclear.The aim of this study was to comprehensively investigate the protective potential and mechanisms of vine tea in high-fat diet rat through a combination of in vivo and in vitro experiments.The efficacy of vine tea was evaluated using a high-fat diet rat model and an oxidized low-density lipoprotein-treated cell model,with physiological and biochemical indicators measured in rat serum and cell supernatants.Transcriptomics was utilized to investigate alterations mRNA expression following the administration of dihydromyricetin in cell model.Metabolomics and 16S rRNA sequencing was employed to examine changes in metabolites in the serum and changes in gut microbiota of high-fat diet rats after administering vine tea extract.Vine tea extract and dihydromyricetin can reduce elevated levels of lipids,including total cholesterol and triglycerides,following modeling.Transcriptomic data indicate that dihydromyricetin exerts its effects by regulating ferroptosis signaling pathways.Metabolomic analysis demonstrates that the administration of vine tea extract influences the vitamin K cycle and glutathione,thereby alleviating the progression of ferroptosis.Additionally,16S rRNA sequencing reveals that vine tea extract increases Lactobacillaceae in the gut microbiota,which subsequently affects the levels of lysophosphatidylcholine,a major phospholipid component of oxidized low-density lipoprotein in serum.Our results indicate that vine tea can regulate ferroptosis signaling pathways and increase Lactobacillaceae in the gut microbiota,thereby exhibiting cardiovascular protective effects in high-fat diet rats.
基金National Natural Science Foundation of China(81673727)。
摘要Uncovering the underlying process of epileptogenesis is crucial for developing effective treatment strategies for epilepsy.However,the cellular and molecular changes throughout epileptogenesis are not fully understood.In this study,single-nucleus RNA sequencing was performed on the hippocampus,temporal cortex,and thalamus across the acute,latent,and chronic phases in a pilocarpine-induced rat model and controls.We created a comprehensive single-nucleus transcriptomic atlas of rat epileptogenesis,consisting of 311,177 single nuclei.Our analysis revealed distinct transcriptional signatures across the three phases and regions,including significant gene expression changes in the acute phase and critical synaptic and neural network remodeling in the thalamus during the latent phase.Notably,we identified two novel astrocyte clusters during epileptogenesis,with the EX-Astro C3-IN pathway emerging as a potential intervention target.The dataset provides a detailed understanding of the dynamic cellular and molecular landscape of epileptogenesis.
基金Outstanding Young Investigator Program of Capital Medical University,Grant/Award Number:A2308。
摘要Phrenic nerve stimulation(PNS)may preserve diaphragm activation and mitigate multiorgan injury during mechanical ventilation(MV);however,a minimal invasive rat model integrating PNS with MV is lacking.We established an omohyoid muscle-based PNS rat model combined with MV.Bilateral nerves were exposed within 20±2 min by transection at the intermediate tendon of omohyoid muscle,minimizing trauma and bleeding.Threshold stimulation(0.6±0.2 mA)correlated with body weight.Ventilator-synchronized stimulation increased compound muscle action potentials by~30%,whereas histology confirmed intact nerve.Physiological parameters remained stable throughout ventilation.This model provides a safe and scalable platform for mechanistic and preclinical studies on PNS-mediated protection against MV-induced organ injury.
摘要[Objectives]To investigate the mechanism by which Dachaihu Decoction affects visceral pain behavior in a rat model of ulcerative colitis(UC).[Methods]Twenty-one male Sprague-Dawley(SD)rats were randomly and equally divided into a control group,a UC group,and a Dachaihu Decoction group(n=7 per group).After treatment completion,visceral pain behavior and colonic motility indices were assessed using in vivo colorectal distension(CRD)and abdominal withdrawal reflex(AWR)tests.[Results]Compared to the UC group,the Dachaihu Decoction group exhibited increased colon length,elevated colonic basal tension,heightened peak contractile tension,and increased contraction frequency.These differences were statistically significant(P<0.05).[Conclusions]Dachaihu Decoction may ameliorate visceral hyperalgesia induced by rectal distension stimuli in the UC rat model by improving colonic motility.
摘要Objective:To establish a liquid chromatography tandem mass spectrometry(HPLC-MS/MS)method to determine amygdalin and paeoniflorin in rat blood serum.Method:After protein precipitation by acetonitrile,a gradient elution procedure was performed to separate the samples by using acetonitrile and ammonium acetate buffer as the mobile phase.The quantitative determination was based on an HPLC-MS/MS in negative electron spray ionization mode and in multiple reaction monitoring(MRM)mode.The precursor to product ion transitions for amygdalin and paeoniflorin were 456.2 to 323.1 and 479.2 to 121.0,respectively.Results:The linear ranges of amygdalin and paeoniflorin were 1-300 ng/mL(rAmy=0.9994,rPae=0.9993)with the lowest limits of quantification were 0.3 ng/ml.The extract recovery of amygdalin and paeoniflorin were 91.1%,94.2%,92.0%and 90.3%,93.7%,94.1%at concentrations of 3,20,100 ng/mL,respectively.All the intra and inter day precisions of analysis were less than 15%,and the RE were in the range of±15%.Conclusion:The method is specific,sensitive,accurate,and suitable for determination of amygdalin and paeoniflorin in rat blood serum.
基金Leducq Trans-Atlantic Network of Excellence,Grant/Award Number:TNE-21CVD04Spanish Ministry of Science and Innovation,Grant/Award Number:PID2020-117765RB-I00 and PID2022-140616OB-I00+1 种基金Instituto de Salud Carlos Ⅲ,European Development Regional Fund,RICORS-ICTUS Grant/Award Number:RD21/0006/0001the FORTALECE program. Grant/Award Number:FORT23/00023。
摘要Stroke induces profound neuroinflammation and systemic immune dysregulation,including disturbances in gut homeostasis.Experimental evidence suggests that intestinal barrier permeability(IBP)and bacterial translocation(BT)critically influence stroke outcomes.However,biological variability among commonly used rodent substrains has received limited attention.In this pilot study,we compared poststroke immune responses in two Wistar rat substrains obtained from different suppliers:RccHan(Envigo)and RjHan(Janvier).Naive animals(n=4)and rats subjected to permanent cerebral ischemia(n=8 per substrain)were evaluated 72 h after middle cerebral artery occlusion and stratified according to the presence or absence of BT.Immune cell populations in blood and bone marrow were analyzed using flow cytometry,and leukocyte infiltration into ischemic brain tissue was quantified using immunohisto-chemistry.Differences were considered statistically significant when p<0.05.Both substrains developed significant infarcts and neurological deficits.RccHan rats exhibited larger infarct volumes and more extensive BT across multiple organs.In contrast,RjHan rats exhibited BT mainly confined to mesenteric lymph nodes but exhibited greater IBP.Although dissemination was broader in RccHan rats,overall bacterial burden was slightly lower compared with RjHan,and extraintestinal bacterial composition differed between groups.Particularly,RjHan rats exhibited stronger systemic and central immune activation,with significant alterations in lymphocyte and monocyte populations and enhanced granulocyte and T-cell infiltration within ischemic lesions.These findings demonstrate that substrain origin profoundly influences poststroke intestinal barrier integrity,bacterial dissemination,and immune responses considering substrain-related variability is essential to improve reproducibility and translational relevance in preclinical stroke research.
摘要AIM:To examine the ocular toxicity linked to sildenafilusage and the possible protective benefits of adenosinetriphosphate(ATP)against this toxicity in rats.METHODS:Twenty-four male albino Wistar-type ratswere divided into four equal groups(n=6/group)as follows:healthy group(HG),ATP-only group(ATPG),sildenafil-onlygroup(SILG),and ATP+sildenafil group(ATP+SLD).ATPG andATP+SLD groups were injected intraperitoneally with ATP(4 mg/kg),while SILG and HG groups were injected withsaline(0.9%NaCl)by the same route as a solvent.One hourafter the administration of ATP and solvent,sildenafil(10 m g/k g)was administered orally to the SILG andATP+SLD groups.This procedure was repeated once a dayfor 4wk.The animals were then sacrificed,eyeballs wereremoved and oxidant and antioxidant parameters weremeasured biochemically.Additionally,the ocular tissueswere evaluated histopathologically.RESULTS:Sildenafil increased oxidant(malondialdehyde)levels and decreased antioxidant levels(total glutathione,superoxide dismutase,catalase)in rat ocular tissues andcaused severe oxidative stress.In addition,sildenafil hasbeen shown histopathologically to cause oxidative damagein retinal layers.ATP treatment suppressed oxidative stressand attenuated histopathological damage in the retinal layers.CONCLUSION:ATP protects retinal tissue againstsildenafil-induced ocular oxidative damage in rats andmay contribute to the development of novel approaches toprevent or treat this damage.
基金Chilean National Agency for Research and Development(ANID,Agencia Nacional de Investigación y Desarrollo)FONDECYT de Iniciación,Grant/Award Number:11241417 and 11251077。
摘要The simultaneous characterization of histological alterations and distinct celldeath pathways associated with diabetic cardiomyopathy(DCM)has not beencomprehensively explored and may differ depending on the experimental model.Weevaluated cardiac histological changes and markers of apoptosis,cell death associatedwith mitochondrial permeability transition pore(mPTP)opening(necrosis),andautophagy in early and advanced stages of streptozotocin(STZ)-induced diabetesin rats receiving insulin daily to prevent mortality while maintaining hyperglycemia.Adult male Sprague–Dawley rats(n=4–5)were randomly assigned to receive STZ(diabetic group)or saline(mock)and followed up for 4 or 12 weeks.Hearts wereprocessed for histological examination and immunohistochemical detection of activecaspase-3,beclin-1,and cyclophilin D.STZ significantly increased glycemia at bothtime points,whereas body weight reduction was observed only at 12 weeks.Noevidence of cardiac hypertrophy,fibrosis,or structural injury was detected in diabeticrats at either stage.Expression of caspase-3,beclin-1,and cyclophilin D decreased at12 weeks compared with 4 weeks,regardless of treatment;however,cyclophilin D waselevated in diabetic hearts at 4 weeks.These results suggest an early susceptibilityto mPTP opening under persistent hyperglycemia,despite the absence of overthistological damage.They also underscore the critical importance of insulin dosingand study duration when interpreting data from STZ-based models.Further studiesare warranted to determine how even minimal insulin administration may shape thetemporal dynamics of cell death during the progression of DCM.
基金National Research Foundation,Grant/Award Number:129530。
摘要Background:Atherosclerosis begins with dyslipidemia,vascular inflammation,and en-dothelial dysfunction.Rodent models that capture these early events are needed for mechanistic and interventional studies.This study evaluated whether a cholesterol-rich,high-fat diet(HFD)supplemented with vitamin D and propylthiouracil(PTU)promotes a pro-atherogenic phenotype in rats,as evidenced by dyslipidemia,inflam-mation,markers of endothelial dysfunction,and early vascular remodeling.Methods:Male Sprague-Dawley rats(n=18)received standard chow or a HFD con-taining 2%cholesterol,3%lard,0.5%cholate,vitamin D(200000 IU/kg),and PTU(0.2%w/w)for 11 weeks.Terminal serum total cholesterol,high-density lipoprotein,low-density lipoprotein(LDL)/very low-density lipoprotein(VLDL),triglycerides,calcium,interleukin-6(IL-6),C-reactive protein,serum amyloid A(SAA),circulating endothelial nitric oxide synthase(eNOS),and intracellular adhesion molecule-1(ICAM-1)were measured.The aorta,the coronary arteries,and the liver were examined histologically.Results:HFD-fed rats developed significant hypercholesterolemia with higher total cholesterol and LDL/VLDL(p<0.0001)and lower triglycerides(p<0.0001)versus controls.Serum calcium was higher(p<0.0001)without vascular calcification.Aortae exhibited wall thickening,smooth-muscle disarray,mononuclear infiltrates,and focal foam cell-like changes;coronary arteries exhibited endothelial irregularities and perivascular infiltrates.Livers exhibited micro-and macrovesicular steatosis.IL-6 and SAA were higher(p<0.05),and circulating eNOS was lower(p<0.05);ICAM-1 did not differ significantly.Conclusion:An 11-week vitamin D/PTU-supplemented HFD induces an LDL-dominant dyslipidemia with systemic inflammation and evidence consistent with endothelial dysfunction,alongside histological features of early vascular remodeling and hepatic steatosis.This nongenetic model may be useful for studying early atherogenic changes.
摘要BACKGROUND Chronic radiation proctitis(CRP),a major complication of pelvic radiotherapy,lacks effective treatments and a standardized animal model that recapitulates its late fibrotic and angiogenic pathologies.AIM To establish a model that recapitulates the features of human CRP and to investigate the mechanisms of irreversible tissue damage.Rats were randomized into a control group and single-dose irradiation groups(12.5-37.5 Gy).Rectal injury was assessed via 6-month continuous endoscopic observation,the modified Vienna Rectoscopy Score,and histological analysis.Additionally,rectal tissues were analyzed for cytoskeletal protein alterations.RESULTS Acute mucosal injury was reversible at doses below 20 Gy.In the 20-35 Gy groups,persistent radiation proctitis,marked telangiectasia,and severe mucosal fibrosis indicated irreversible injury.Furthermore,cytoskeletal proteins,particularly tubulin,decreased sharply at doses≥20 Gy.Vascular endothelial growth factor was mildly upregulated mainly in the deep tissue layers during the acute phase,whereas it was significantly increased in the mucosa of the highdose groups during the chronic phase.CONCLUSION Single-dose radiation(20-35 Gy)induces CRP.Reduced tubulin expression marks the early transition to chronic injury(P<0.0001).
摘要AIM:To investigate the effects of zingerone(ZO)on the retina in diabetic rats.METHODS:A total of 70 rats were randomly selected and divided into seven groups[diabetic group(Dm+;n=10),diabetic+metformin group(Dm+Met;n=10),diabetic+ZO25 group(Dm+ZO25;n=10),diabetic+ZO50 group(Dm+ZO50;n=10),diabetic+metformin group+ZO 50 Group(Dm+Met+ZO50;n=10)].Diabetes was induced by streptozotocin(STZ),and metformin and two different doses of ZO were administered via gavage.Retinal tissues were evaluated by histopathological and immunohistochemical analyses.RESULTS:In diabetic rats,severe retinal inflammation,tissue necrosis,and increased tumor necrosis factor-α(TNF-α)expression were observed.ZO administration reduced these effects in a dose-dependent manner.Protective effects of metformin alone were limited,and no synergistic benefit was observed in ZO+Met groups.Administration of 50 mg/kg ZO to non-diabetic rats caused no retinal toxicity.Additionally,elevated 8-OHdG and c-Jun N-terminal kinase(JNK)expressions in diabetic retinopathy models were significantly reduced by ZO treatment.CONCLUSION:ZO can markedly reduce the pathological effects of the retina in a diabetic rat model.
摘要BACKGROUND Spinal cord ischemia-reperfusion injury(IRI),which can occur as a result of temporary aortic occlusion during resection of thoracoabdominal aneurysms,can be an unpredictable and devastating complication of aortic surgery.There are no specific medications or guidelines for the prevention and treatment of spinal cord IRI(SCIRI).It is now known that IRI not only exacerbates local tissue damage when blood flow is restored but also affects distant organs,such as the liver,lungs,and brain,through mediators released into the systemic circulation.Studies show that ozone pretreatment reduces oxidative damage by increasing antioxidant capacity,promotes anti-inflammatory signaling,improves blood circulation,and ameliorates IRI.Our study is one of the first to examine the effects of ozone on remote organs(liver,lung,and brain)when administered via different routes(intrathecal,intraperitoneal,rectal)in a spinal cord ischemia-reperfusion model.AIM To determine whether ozone administered by different routes offers multiorgan protection in SCIRI.METHODS Thirty adult Wistar albino rats were randomly divided into five groups(n=6,each):A control(C group),an IR group,an IR rectal ozone(IRRO)group,an IR intrathecal ozone(IRITO),and an IR intraperitoneal ozone(IRIPO).In the IR groups,the spinal cord IR models(a 30-minute ischemia period was applied to the infrarenal abdominal aorta using an atraumatic vascular clamp,and then a 120-minute reperfusion period was applied by removing the clamp)were applied.An ozone-oxygen mixture of 1 mg/kg(50μg/mL)was administered by rectal insufflation to the IRRO group,0.7 mg/kg(50μg/mL)via the peritoneum to the IRIPO group,and 20μL(20μg/mL)intrathecally to the IRITO group 30 minutes before midline laparotomy.At the end of the reperfusion procedure,histopathological and biochemical analyses of liver,lung,and brain tissues were performed.RESULTS Liver tissue malondialdehyde(MDA)levels were significantly lower,and catalase(CAT)enzyme activities were significantly higher in the IRRO,IRITO,and IRIPO groups than in the IR group.Histopathologically,we had favorable results from all three ozone applications compared to the IR group.Lung tissue MDA levels were significantly lower,and CAT enzyme activities were significantly higher in the IRITO and IRIPO groups than in the IR group.We had more positive results in the IRRO group than in the IR group,but the difference was not found to be significant.Histopathologically,we obtained significantly more positive results in the IRITO and IRIPO groups compared with the IR group regarding all the criteria we evaluated.Our results in the IRRO group were also positive.Brain tissue MDA levels were significantly lower and CAT enzyme activities significantly higher in the IRITO and IRIPO groups than in the IR group.We had positive results in the IRRO group compared with the IR group.Histopathologically,we obtained significantly more positive results in the IRITO group regarding all the criteria we evaluated.CONCLUSION We observed histopathologically that single-dose ozone pretreatment administered intrathecally,intraperitoneally,or rectally had positive effects on liver,lung,and brain tissues compared to the IR group in an SCIRI model in rats due to its antioxidant effect.The best histopathological results were obtained with intrathecal,intraperitoneal,and rectally administered ozone,in that order,in all three tissues.
摘要BACKGROUND Diabetes is an endocrinopathy characterized by the inability to produce insulin or insufficient insulin production because of the destruction of beta cells in the pancreas caused by autoimmune or other epidemiological factors.Diabetes can lead to physical and psychological complications.AIM To investigate early behavioral changes in an experimental diabetes model in juvenile rats.METHODS In this study,a total of 14 juvenile male Wistar rats(7 rats per group)were used.To induce the diabetes model,120 mg/kg streptozotocin(STZ)was administered,while the control group received 1 mL/kg physiological saline.The open field test and the hole-board test were performed for five minutes each.Unpaired comparisons were evaluated using Student’s t test or the Mann-Whitney U test.Correlations were analyzed using the Pearson test.RESULTS Severe hyperglycemia was observed in rats in the diabetes mellitus model induced by STZ,and all diabetic rats displayed glucose levels above 400 mg/dL.In the open-field test,the time spent in the central area,the number of rearings,and the total distance traveled were significantly lower in diabetic rats than in naive rats(P<0.05).In the hole-board test,the duration and frequency of total head dipping were considerably lower in diabetic rats than in healthy rats(P<0.01).The grooming time(P<0.01)and freezing time(P<0.0001)increased dramatically in the diabetes mellitus group.A remarkable correlation was found between behavioral changes and hyperglycemia.CONCLUSION Our data indicate that early-stage diabetes induced by STZ increases anxiety-like behaviors and impairs exploratory behaviors.These behavioral changes may also occur in children with undiagnosed or untreated hyperglycemia and can provide important clues in clinical practice.
摘要[Objectives]To observe the effect of Shenfu Injection on regional cerebral blood flow(RCBF)in a rat model of acute cerebral infarction.[Methods]Thirty Sprague-Dawley(SD)rats were randomly assigned to three groups:control group,model group,and Shenfu Injection group(administered via tail vein injection at 2 mL/100 g body weight).The model was established using the middle cerebral artery occlusion(MCAO)method,and electroencephalogram(EEG)spike amplitude and RCBF were measured at 0,30,and 60 min,as well as 1,3,and 6 d post-reperfusion.[Results]Compared with the model group,the Shenfu Injection group exhibited significantly increased RCBF on day 3 and 6(P<0.05)and significantly decreased EEG spike amplitude on day 1,3,and 6(P<0.05).[Conclusions]Shenfu Injection improves regional cerebral blood flow in rats with acute cerebral infarction,potentially through mechanisms involving suppression of abnormal electrical discharges and dilatation of microvessels.