mTOR信号通路在马桑内酯点燃大鼠难治性癫痫模型中的作用

Correlation study of mTOR pathway and pharmacoresistance of Sprague-Dawley rat epilepsy model kindled by coriaria lactone

目的 探究哺乳动物雷帕霉素靶蛋白(Mammalian target of rapamycin,mTOR)信号通路在马桑内酯点燃Sprague-Dawley大鼠难治性癫痫模型中的作用.方法 选取60只8~10周SD大鼠为研究对象,随机分为实验组(n=50)和对照组(n=10).实验组给予马桑内酯1.75 mg/kg肌注,1次/84h,给药间期达到5次以上5级发作即纳入点燃组;对照组同时给予等体积生理盐水.取大鼠脑组织,采用免疫组织化学检测两组P-S6的蛋白表达水平,计数阳性细胞数,并行统计学分析.结果 实验组共点燃大鼠40只,点燃率为80%.对照组CA1区和CA2区仅有少量星形胶质细胞表达P-S6,神经元少有表达;点燃组CA1和CA3区有大量P-S6高表达细胞,且主要集中在星形胶质细胞,神经元阳性细胞数也增加,点燃组CA1和CA3区阳性细胞数均高于对照组阳性细胞数,差异有统计学意义(P<0.001).在海马DG区,对照组仅有少量颗粒细胞表达P-S6,而点燃组颗粒细胞及神经元阳性细胞数明显增加,差异有统计学意义(t=12.816,P<0.001).结论 mTOR信号通路活化可能与马桑内酯点燃SD大鼠难治性癫痫模型密切相关.

Objective To investigate the association between mTOR pathway and pharmacoresistance of Sprague-Dawley rat epilepsy model kindled by coriaria lactone.Methods A kindling model of pharmacoresistant temporal lobe epilepay was developed by injecting Sprague-Dawley(SD)rats with coriaria lactone(CL)(1.75 mg/kg,every 84 h).Normal SD rats were injected with normal sodium(NS)served as control group.Rats with five or more consecutive stage 5 scizures were included in kindled group.Immunohistochemistry was used to detect the levels of P-S6 in both groups.Results The expressions of P-S6 in CA1 and CA3 were significantly higher compared with control group,and were mainly in astrocytes(P<0.001).In addition,the expression of P-S6 in DG area was significantly higher than that in control group,with more granular cell and neuron(P<0.001).Conclusions The mTOR pathway may be corrclated with the drug resistance of refractory lobe cpilepsy kindled by coriaria lactone.