右美托咪定激活miR-211抑制线粒体凋亡减轻脑缺血再灌注脑损伤

Dexmedetomidine attenuates cerebral ischemia-reperfusion injury by inhibiting mitochondrial apoptosis by activating miR-211

目的 探讨右美托咪定在脑缺血再灌注损伤中的相关作用机制。方法 采用线栓法制备SD大鼠大脑中动脉闭塞再灌注(I/R)模型,将大鼠按照随机数字法分为假手术组(Sham组)、模型组(I/R组)和右美托咪定给药组(Dex组);于术后24h对各组大鼠进行组织病理学的检测;采用TUNEL染色法检测大鼠脑细胞的凋亡情况;采用ELISA检测S-100β和NSE的水平变化;采用免疫荧光法对ROS水平进行检测;应用qPCR检测miR-211的表达;Western blot方法检测Bcl-2、Bax、Cyt C和caspase3的表达状况。结果 Dex可以改善大脑病理学损伤;降低大鼠脑细胞的凋亡;降低S-100β、NSE和ROS的含量;促进miR-211的表达;促进Bcl-2的表达,抑制Cyt C、Bax、Caspase-3的表达和Bax/Bcl-2的比值。结论 右美托咪定通过激活miR-211降低脑缺血再灌注后损伤,其机制与抑制线粒体相关的凋亡蛋白有关。

Objective To investigate the mechanism of dexmedetomidine in cerebral ischemia/reperfusion injury in rats. Methods The middle cerebral artery occlusion reperfusion(I/R) model of SD rats was prepared by using thread embolization method. SD rats were randomly divided into sham group, I/R group and Dex group according to the random number method. The histopathological changes of rats in each group were detected at 24 hours after operation. The apoptosis of brain cells was detected by TUNEL staining. The expression of S-100β and NSE was detected by ELISA. The level of ROS was detected by immunofluorescence. The expression of miR-211 was detected by qPCR. The expression of Bcl-2, Bax, Cyt C and caspase-3 was detected by Western blot. Results Dex medetomidine can improve the pathological damage of brain;reduce the apoptosis of brain cells;reduce the content of S-100β, NSE and ROS;promote the expression of miR-211;promote the expression of Bcl-2;inhibit the expression of Cyt C, Bax, caspase-3 and the ratio of Bax/Bcl-2.Conclusion Dexmedetomidine can reduce cerebral ischemia/reperfusion injury by activating miR-211, which is related to the inhibition of mitochondrial apoptosis protein.