AIF线粒体核转位在异丙酚全脑缺血再灌注损伤大鼠脑保护作用中的研究

神经元凋亡是脑缺血再灌注损伤神经功能丧失的主要原因，凋亡诱导因子（AIF）线粒体核转位介导的以细胞核内染色质凝集和大规模的DNA断裂为主要表现的Caspase非依赖性凋亡在该过程中起重要作用。但该过程是否参与异丙酚抗神经元凋亡的脑保护作用，迄今国内外尚无报道。本课题组前期研究发现，异丙酚可上调Bcl-2/Bax比值抑制神经元凋亡，但并未研究其抗凋亡的具体机制及AIF在该过程所起的作用。本研究采用二血管夹闭法建立大鼠全脑缺血再灌注损伤模型，给予Z-VAD-FMK阻断Caspase依赖神经元凋亡途径，并采用病理形态学、透射电镜、分子生物学、流式细胞仪等技术，观察异丙酚脑保护作用，及其脑保护机制是否与通过上调Bcl-2/Bax比值，抑制MPTP开放，抑制AIF介导的Caspase非依赖途径的神经元凋亡有关。本课题深入探讨异丙酚脑保护作用的线粒体机制，为临床脑保护策略提供新的方法和理论基础。

Neuron apoptosis is the main reason for the loss of nerve function in cerebral ischemia/reperfusion injuty. Apopotosis induced factor(AIF) mitochondrial nuclear transfer mediated by nuclear chromatin agglutination and large-scale DNA fracture as the main performance of Caspase undependent passway in the process of apoptosis plays an important role. Weather this process is important in brain protective effect of propofol is still unknown. Our previous studies found that propofol can adjust the Bcl - 2 / Bax ratio, inhibition of Caspase depend on the way of neuron apoptosis. However, if brain protection of propofol has relationship with AIF mediated Caspase undependent apoptosis, has not been reported at home and abroad. This study used two vascular blocked method to establish the rat whole brain ischemia reperfusion injury model, given Z-VAD-FMK to block the Caspase dependent apopotosis, using the pathological morphology and transmission electron microscopy, molecular biology, flow cytometry technology, observe the propofol brain protection, and if brain protection mechanism of propofol has relationship with raising of Bcl - 2 / Bax ratio, reducing of MPTP open, restrain of AIF induced Caspase undependent neuron apoptosis. This study will clarify propofol brain protection mitochondrial mechanism for future clinical brain protection to provide new methods and strategies.