α-细辛醚对氯化锂-匹罗卡品致痫大鼠PI3K/Akt/mTOR通路的调节作用

Regulation effects of alpha-asarone on PI3K/Akt/mTOR pathway in lithium chloride pilocarpine induced epileptic rats

目的 探讨α-细辛醚对癫痫大鼠学习记忆的影响及分子机制.方法 SD大鼠随机分成生理盐水组、癫痫组、α-细辛醚组,采用氯化锂-匹罗卡品注射诱导大鼠癫痫造模,α-细辛醚组造模前用α-细辛醚干预28 d.水迷宫检测大鼠空间学习记忆能力,Western blot方法检测大鼠海马组织PI3K、Akt、mTOR蛋白表达,采用RT-PCR技术检测大鼠海马组织PI3K、Akt、mTOR的mRNA表达.结果 水迷宫实验结果显示α-细辛醚能够改善大鼠的学习记忆能力;Western blot结果显示,癫痫组海马组织PI3K、p-Akt、mTOR蛋白表达较生理盐水组降低（P〈0.05）,α-细辛醚组海马组织的各蛋白表达较癫痫组增加（P〈0.05）.RT-PCR结果显示,癫痫组海马组织PI3K、p-Akt、mTOR mRNA表达水平与生理盐水组比较显著降低（P〈0.05）,α-细辛醚组海马组织PI3K、p-Akt的mRNA表达水平与癫痫组比较显著增高（P〈0.05）.结论 α-细辛醚能够改善氯化锂-匹罗卡品致痫大鼠学习记忆,其分子机制可能与上调PI3K/Akt/mTOR表达有关.

Objective To explore the molecular mechanism of alpha-asarone to affect learning and memory skills of lithium chloride pilocarpine induced Epileptic Rats. Methods SD rats were randomly divided into 3 groups： normal saline group, epilepsy group, and alpha-asarone group. Lithium chloride pilocarpine injection were applied to induce rat epilepsy models. The rats of the alpha-asarone group were given alpha- asarone 28 days before modeling. Water maze was used to detect the spatial learning and memory ability of the SD rats. Western blot technique was used to detect the expressions of PI3K, Akt and mTOR proteins of hippocampus in lithium chloride pilocarpine induced epileptic rats. RT-PCR technique was used to detect the expressions of PI3K, Akt and mTOR mRNA of hippocampus in lithium chloride pilocarpine induced epileptic rats. Results Water maze test result showed that alpha-asarone can improve the spatial learning and memory ability of the SD rats. The expression of PI3K, Akt and mTOR proteins decreased obviously in epilepsy group compared with those in saline group （P 〈 0.05）. The expressions of PI3K, Akt and mTOR proteins increased obviously in alpha-asarone group compared with those in epilepsy group （P 〈 0.05）. The results of RT-PCR technique showed that the expressions of PI3K, p-Akt and mTOR mRNA decreased obviously in epilepsy group compared with those in saline group （P 〈 0.05）, and the expressions of PI3K and p-Akt mRNA increased obviously in alpha-asarone group compared with those in epilepsy group （P 〈 0.05）. Conclusions Alpha-asarone can improves learning and memory of lithium chloride pilocarpine induced epileptic rats, and the molecular mechanism maybe related to up-regulation of the expressions of PI3K, Akt and roTOR proteins and mRNA.