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-  2016 

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

Keywords: 哺乳动物帕霉素靶蛋白,癫痫形成,雷帕霉素,炎性因子

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Abstract:

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

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