mTOR信号抑制剂对幼鼠痫性发作后早期炎性因子的影响  

Effect of mTOR Signaling Inhibitors on the Early Inflammatory Factors in Immature Rats After Epileptic Seizures

作　　者：张海菊[1] 姚宝珍[1] 张晓[1] 凌伟[1] 

机构地区：[1]武汉大学人民医院儿科,湖北武汉430060

出　　处：《武汉大学学报（医学版）》2016年第2期209-212,217,共5页Medical Journal of Wuhan University

基　　金：武汉大学人民医院青年基金孵化项目(编号:RMFH 0001)

摘　　要：目的:探讨mTOR抑制剂对幼鼠痫性发作后早期炎性因子的影响,为预防慢性癫痫形成寻找新的途径。方法:侧脑室注射海人藻酸(KA)诱导幼鼠(P10d)痫性发作(SE),mTOR抑制剂雷帕霉素(RAP)在SE发作后4h腹腔注射给药进行干预1周。分为KA组,KA+RAP组及生理盐水对照组(NS组)。观察慢性期自发性癫痫(SRS)发生率在各组的差异。痫性发作1周后实时定量RT-PCR检测炎性因子白细胞介素1-β(IL-1β)、转移生长因子-1(TGF-1)及环氧合酶-2(COX-2)在各组的表达差异。SE发作后2周Western blotting检测上述3种炎性因子蛋白表达水平在各组的差异。结果:在KA组,20只幼鼠中有14只观察到SRS发作,SRS发生率为70%,而在KA+RAP组中,21只幼鼠中有10只观察到SRS发生,发生率为47.6%,RAP干预明显降低慢性期SRS的发生率(P<0.05)。SE发作后1周IL-1β、TGF-1和COX-2基因表达水平在KA组表达明显增高,KA+RAP干预组较KA组减低,但较NS组表达增高。SE发作后2周IL-1β、TGF-1和COX-2基因表达水平在KA组表达明显增高,KA+RAP干预组较KA组减低,但较NS组表达增高。三种炎性因子表达水平在三组呈现相似变化趋势。结论:mTOR抑制剂能减少慢性期SRS的发生,抑制痫性发作后早期炎性因子IL-1β、TGF-1和COX-2基因和蛋白水平的表达。可能为预防慢性癫痫的形成提供新的思路和途径。Objective： To investigate the effect of roTOR inhibitor on early inflammatory factors in im mature rats after epileptic seizures （SE） and find a new way for the prevention of chronic epilep- c genesis. Methods. Seizures were induced in rats （P10d） by intracerebroventric^lar injection kaini- cacid （KA）, and mTOR inhibitor rapamycin intraperitoneal injection for 1 week after SE 4 hours. The experiment rats were divided into KA group, KA＋RAP group and NS group. The differ- ence of chronic spontaneous seizures （SRS） occurred in the groups. Real time quantitative RT- PCR was used to detect the gene expression of inflammatory cytokine interleukin 1- beta （IL-1 beta）, transforming growth factor -1 （TGF-1） and cyclooxygenase -2 （COX-2） in the different groups after 1 week after seizures. Western blotting was used to detect the expression protein level of the above 3 kinds of inflammatory factors. Results： In group KA, 20 rats were observed in 14 episodes of SRS, the incidence rate of SRS was 70%, while in group KA＋RAP, 21 rats were observed in 10 SRS, the incidence rate was 47.6%, RAP treatment significantly reduced the incidence of SRS in chronic phase （P〈0.05）. The gene expression level of IL-1 beta, TGF 1 and COX-2 in KA group increased significantly after seizures. Compared with KA group, the gene ex- pression of the three inflammation factors in KA%RAP group decreased, which were higher than those in the NS group. After 2 weeks, the expression of IL-1β, TGF-1 and COX-2 protein ex- pression levels in KA group increased significantly after seizures. The expression levels in KA＋ RAP group were lower than that in KA group, but also higher than that in NS group. The differ- ence was significant. The expression of inflammatory factor levels in the three groups showed a similar variation trend. Conclusion： mTOR inhibitors can reduce the occurrence of SRS in chronic phase, and inhibit the gene and protein expression of early inflammatory cytokines of IL-1, TGF- 1 and COX-2

关 键 词：哺乳动物帕霉素靶蛋白 癫痫形成 雷帕霉素 炎性因子 

分 类 号：R741.02[医药卫生—神经病学与精神病学]