Pain consists of sensory-discriminative and emotional-affective components.The anterior cingulate cortex(ACC)is a critical brain area in mediating the affective pain.However,the molecular mechanisms involved remain la...Pain consists of sensory-discriminative and emotional-affective components.The anterior cingulate cortex(ACC)is a critical brain area in mediating the affective pain.However,the molecular mechanisms involved remain largely unknown.Our recent study indicated that C-X-C motif chemokine 13(CXCL13)and its sole receptor CXCR5 are involved in sensory sensitization in the spinal cord after spinal nerve ligation(SNL).Whether CXCL13/CXCR5 signaling in the ACC contributes to the pathogenesis of pain-related aversion remains unknown.Here,we showed that SNL increased the CXCL13 level and CXCR5 expression in the ACC after SNL.Knockdown of CXCR5 by microinjection of Cxcr5 shRNA into the ACC did not affect SNL-induced mechanical allodynia but effectively alleviated neuropathic painrelated place avoidance behavior.Furthermore,electrophysiological recording from layer Ⅱ-Ⅲ neurons in the ACC showed that SNL increased the frequency and amplitude of spontaneous excitatory postsynaptic currents(sEPSCs),decreased the EPSC paired-pulse ratio,and increased the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor/N-methyl-D-aspartate receptor ratio,indicating enhanced glutamatergic synaptic transmission.Finally,superfusion of CXCL13 onto ACC slices increased the frequency and amplitude of spontaneous EPSCs.Pre-injection of Cxcr5 shRNA into the ACC reduced the increase in glutamatergic synaptic transmis sion induced by SNL.Collectively,these results suggest that CXCL13/CXCR5 signaling in the ACC is involved in neuropathic pain-related aversion via synaptic potentiation.展开更多
目的观察趋化因子CXCL13及其受体CXCR5在结直肠癌转移灶中的表达变化,探讨其与结直肠癌转移及KRAS基因突变的关系。方法选择97例结直肠癌组织标本(观察A组)、51例淋巴结转移灶标本(观察B组),同时选择52例正常结直肠标本(对照A组)和43例...目的观察趋化因子CXCL13及其受体CXCR5在结直肠癌转移灶中的表达变化,探讨其与结直肠癌转移及KRAS基因突变的关系。方法选择97例结直肠癌组织标本(观察A组)、51例淋巴结转移灶标本(观察B组),同时选择52例正常结直肠标本(对照A组)和43例正常淋巴结标本(对照B组)。用免疫组织化学法检测CXCL13及CXCR5蛋白在上述组织中的表达,分析其与临床病理参数、患者生存时间之间的关系。用Real Time PCR法检测148例结直肠癌组织KRAS基因突变情况,并分析其与CXCL13及CXCR5蛋白表达的关系。结果CXCR5在上皮细胞的表达率较高,CXCL13在间质细胞的表达较高。CXCL13及其受体CXCR5蛋白在结直肠癌组织的表达高于正常组织(P<0.05),在转移淋巴结中的表达明显高于正常淋巴结(P<0.05)。在结直肠癌原发灶和淋巴结转移灶中,CXCL13及其受体CXCR5蛋白的表达均具有明显的相关性(P<0.05)。在CXCL13及其受体CXCR5表达的患者中,其中位生存时间明显短于其阴性表达者(P均<0.05)。观察A组KRAS基因突变型36例(其中CXCL13表达阳性12例、CXCR5表达阳性17例),野生型61例(其中CXCL13表达阳性23例、CXCR5表达阳性23例),CXCL13及CXCR5蛋白表达与KRAS基因是否发生突变均有相关性(P均<0.05)。观察B组KRAS基因突变型20例(其中CXCL13表达阳性16例、CXCR5表达阳性14例),野生型31例(其中CXCL13表达阳性8例、CXCR5表达阳性11例),CXCL13及CXCR5蛋白表达与KRAS基因是否发生突变均有相关性(P均<0.05)。结论趋化因子CXCL13及其受体CXCR5蛋白在结直肠组织淋巴细胞的归巢及结直肠癌淋巴结的转移中发挥重要的作用,对预测结直肠癌的转移及评估预后有一定的价值。CXCL13及CXCR5蛋白表达与KRAS基因突变具有较高的一致性。展开更多
基金supported by grants from the National Natural Science Foundation of China (31671091 and 81771197)the Natural Science Foundation of Jiangsu Province, China (BK20171255)the Science and Technology Planning Project of Nantong Municipality, China (MS12017023-9)
摘要Pain consists of sensory-discriminative and emotional-affective components.The anterior cingulate cortex(ACC)is a critical brain area in mediating the affective pain.However,the molecular mechanisms involved remain largely unknown.Our recent study indicated that C-X-C motif chemokine 13(CXCL13)and its sole receptor CXCR5 are involved in sensory sensitization in the spinal cord after spinal nerve ligation(SNL).Whether CXCL13/CXCR5 signaling in the ACC contributes to the pathogenesis of pain-related aversion remains unknown.Here,we showed that SNL increased the CXCL13 level and CXCR5 expression in the ACC after SNL.Knockdown of CXCR5 by microinjection of Cxcr5 shRNA into the ACC did not affect SNL-induced mechanical allodynia but effectively alleviated neuropathic painrelated place avoidance behavior.Furthermore,electrophysiological recording from layer Ⅱ-Ⅲ neurons in the ACC showed that SNL increased the frequency and amplitude of spontaneous excitatory postsynaptic currents(sEPSCs),decreased the EPSC paired-pulse ratio,and increased the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor/N-methyl-D-aspartate receptor ratio,indicating enhanced glutamatergic synaptic transmission.Finally,superfusion of CXCL13 onto ACC slices increased the frequency and amplitude of spontaneous EPSCs.Pre-injection of Cxcr5 shRNA into the ACC reduced the increase in glutamatergic synaptic transmis sion induced by SNL.Collectively,these results suggest that CXCL13/CXCR5 signaling in the ACC is involved in neuropathic pain-related aversion via synaptic potentiation.
摘要目的观察趋化因子CXCL13及其受体CXCR5在结直肠癌转移灶中的表达变化,探讨其与结直肠癌转移及KRAS基因突变的关系。方法选择97例结直肠癌组织标本(观察A组)、51例淋巴结转移灶标本(观察B组),同时选择52例正常结直肠标本(对照A组)和43例正常淋巴结标本(对照B组)。用免疫组织化学法检测CXCL13及CXCR5蛋白在上述组织中的表达,分析其与临床病理参数、患者生存时间之间的关系。用Real Time PCR法检测148例结直肠癌组织KRAS基因突变情况,并分析其与CXCL13及CXCR5蛋白表达的关系。结果CXCR5在上皮细胞的表达率较高,CXCL13在间质细胞的表达较高。CXCL13及其受体CXCR5蛋白在结直肠癌组织的表达高于正常组织(P<0.05),在转移淋巴结中的表达明显高于正常淋巴结(P<0.05)。在结直肠癌原发灶和淋巴结转移灶中,CXCL13及其受体CXCR5蛋白的表达均具有明显的相关性(P<0.05)。在CXCL13及其受体CXCR5表达的患者中,其中位生存时间明显短于其阴性表达者(P均<0.05)。观察A组KRAS基因突变型36例(其中CXCL13表达阳性12例、CXCR5表达阳性17例),野生型61例(其中CXCL13表达阳性23例、CXCR5表达阳性23例),CXCL13及CXCR5蛋白表达与KRAS基因是否发生突变均有相关性(P均<0.05)。观察B组KRAS基因突变型20例(其中CXCL13表达阳性16例、CXCR5表达阳性14例),野生型31例(其中CXCL13表达阳性8例、CXCR5表达阳性11例),CXCL13及CXCR5蛋白表达与KRAS基因是否发生突变均有相关性(P均<0.05)。结论趋化因子CXCL13及其受体CXCR5蛋白在结直肠组织淋巴细胞的归巢及结直肠癌淋巴结的转移中发挥重要的作用,对预测结直肠癌的转移及评估预后有一定的价值。CXCL13及CXCR5蛋白表达与KRAS基因突变具有较高的一致性。