鞘内注射MRS2395对慢性坐骨神经结扎大鼠脊髓背角钙离子接头蛋白-1表达的影响  

Effect of intrathecal MRS2395 on the expression of spinal Iba1 in rats with chronic constriction injury of the sciatic nerve

作　　者：闵娅兰[1] 刘晓红[1] 肖智[1] 刘爱东[1] 田虹[1] 曾俊伟[1] 

机构地区：[1]贵州省遵义医学院基础医学院生理学教研室贵州省麻醉与器官功能保护重点实验室,563000

出　　处：《临床麻醉学杂志》2012年第11期1112-1115,共4页Journal of Clinical Anesthesiology

基　　金：国家自然科学基金资助(31000497);教育部科学技术重点项目(212154)

摘　　要：目的观察鞘内注射P2Y12受体拮抗剂MRS2395对慢性坐骨神经结扎(CCI)大鼠热痛阈及脊髓背角钙离子接头蛋白-1(Iba1)表达变化的影响。方法成年SD大鼠40只,随机均分为五组:假手术组(A组)、CCI模型组(鞘内注射生理盐水,B组)、CCI+鞘内注射MRS2395 1pmol/L组(C组);CCI+鞘内注射MRS2395 10pmol/L组(D组);CCI+鞘内注射MRS2395 100pmol/L组(E组)。B、C、D、E组大鼠均于鞘内置管5d之后行慢性坐骨神经结扎,分别连续14d鞘内注射生理盐水、MRS2395 1、10、100pmol/L,2次/天,分别在术后第1、7、10、14天测定首次给药1h后的热缩足潜伏期(TWL);分别在第7、14天灌注大鼠取脊髓做冰冻切片,观察大鼠脊髓背角Iba1表达的变化。结果术后第1、3、5、7、10、14天B、C、D、E组大鼠TWL明显短于A组,且C、D、E组TWL明显长于B组(P<0.05)。与A组相比,术后第7、14天B、C、D、E组Iba1阳性细胞个数、平均光密度值明显增加(P<0.05)。与B组比较,术后第7、14天C、D、E组脊髓背角Iba1阳性细胞数目明显减少,其平均光密度值明显降低(P<0.05)。结论鞘内注射P2Y12受体拮抗剂MRS2395可以明显抑制CCI大鼠背角小胶质细胞激活和热痛敏症状,提示P2Y12受体拮抗剂可能通过抑制脊髓小胶质细胞的活化而发挥镇痛作用。Objective To investigate the intrathecal effect of MRS2395, a selective P2Y12 receptor anagonist, on thermal withdrawal latency （TWL） and the expression of Ibal in dorsal horn in rats with chronic constriction injury （CCI） of the sciatic nerve. Methods Forty SD rats were randomized into five groups （n = 8）： sham group （group A, sham operation, intrathecal normal saline）, CCI group （group B, CCI＋intrathecal normal saline）, CCI＋1 pmol/L MRS2395 （group C, intrathecal injection of 1 pmol/L MRS2395）, CCI＋10 pmol/L MRS2395 （group D, intrathecal injection of 10pmol/L MRS2395）, CCI＋100 pmol/L MRS2395 （group E, intrathecal injection of 100 pmol/L MRS2395）. Rats in all groups were intrathecally cathetered at 5d before operation. Heat hyperalgesia were evaluated by TWL at 1, 3, 5, 7, 10 and 14 d after surgery. For the rats after ligation, MRS2395 （1, 10 and 100 pmol/L, respectively） or normal saline （10/A） were intrathecally administered twice a day for 14 d. The values of TWL were examined after intrathecal injection. The expression of Ibal in dorsal horn were assessed by immunohistochemistry on 7, 14 post-operative days. Results TWL in group B were significantly lower than that in group A at 1, 3, 5, 7, 10 and 14 d after surgery （P〈0. 05）. Repeated intrathecal administration of MRS2395（1, 10 and 100 pmol/L） markedly suppressed this decrease in TWL compare with group B （P〈0. 05）. Immunohistochemistry showed that the expression of IbM was markedly enhanced in the ipsilateral dorsal horn on days 7 （P 〈0.05） in group B than that in group A. Repeated intrathecal administration of MRS2395（1, 10 and 100 pmol/L） markedly suppressed this increase in Ibal labeling in groups C, D, E than that of group B （P〈0. 05）. Conclusion Activation of P2Y12 receptors in dorsal horn microglia may be a critical event in the pathogenesis of neuropathic pain and suggest that blocking microglial P2Y12 receptors might be a viable therapeutic strategy for treating neuropa

关 键 词：神经病理性疼痛 P2Y12受体 小胶质细胞 

分 类 号：R614[医药卫生—麻醉学]