The protective effect of alpha-lipoic acid against brain ischemia and reperfusion injury via mTOR signaling pathway in rats
The protective effect of alpha-lipoic acid against brain ischemia and reperfusion injury via mTOR signaling pathway in rats
复制标题
α-硫辛酸通过mTOR信号通路对大鼠脑缺血再灌注损伤的保护作用
DOI：
10.1016/j.neulet.2018.02.012
复制
发表时间：
2018-04-03
影响因子：
2.5
通讯作者：
Xie, Rong
中科院分区：
文献类型：
--
作者：
Gao, Xinjie;Chen, Wei;Xie, Rong
α-硫辛酸（ALA）是一种内源性短链脂肪酸，对缺血再灌注损伤具有保护作用。近年来，mTOR信号通路被证实参与了缺血再灌注损伤的发生机制。我们前期的研究证实ALA可以通过mTOR信号通路保护脑血管内皮细胞免受I/R损伤。然而，ALA是否能在体内保护脑I/R损伤及其机制尚不清楚。本研究旨在探讨ALA对脑I/R损伤的保护作用，并进一步证实ALA与mTOR信号通路的关系。dMCAo后给予ALA，建立有或无雷帕霉素预处理的再灌注模型。结果表明，ALA治疗后急性期脑梗死范围明显缩小，神经功能明显改善。脑I/R损伤后mTOR信号通路明显被阻断，ALA处理后mTOR信号通路被激活。而雷帕霉素则可在急性期和长期期消除ALA的保护作用。总之，我们证明了ALA治疗对大鼠脑I/R损伤的保护作用，并且mTOR信号通路是ALA对脑I/R损伤的保护作用所必需的。本研究结果为ALA的临床应用提供了可能，并为缺血性脑卒中提供了潜在的治疗靶点。
Alpha-lipoic Acid(ALA), an endogenous short-chain fatty acid, has been found inducing a protective effect against ischemia and reperfusion(I/R) injury. Recently, mTOR signaling pathway has been proved to involve in the mechanism of I/R injury. In our previous study, we determined that ALA could protect cerebral endothelial cells against I/R injury via mTOR signaling pathway. However, whether ALA can protect against brain I/R injury in vivo and its mechanisms is uncertain. In this study, we try to explore if the ALA treatment can protect against brain I/R injury and confirm the relationship between ALA and mTOR signaling pathway. ALA was administrated to the animals after dMCAo and reperfusion model established with or without rapamycin pre-treatment. The results showed the infarct size was obviously reduced after ALA treatment in acute stage, neurological functions were also improved distinctly. The mTOR signaling pathway was remarkably blocked after brain I/R injury while it could be activated through ALA treatment. However, rapamycin, can abolish the protective effects induced by ALA treatment in both acute and long-term phase. In conclusion, we demonstrate the protective effects induced by ALA treatment against the brain I/R injury in rats and mTOR signaling pathway is required for the protective effects of ALA against brain I/R injury. The results might contribute to the potential clinical application of ALA and provide a potential therapeutic target on ischemic stroke.