深低温停循环（DHCA）术后脑损伤是影响患者预后的重要因素,其发病机制尚未阐明。TLR4信号通路参与缺血再灌注损伤，Occludin是构成血脑屏障（BBB）脑微血管内皮细胞（BMEC）的紧密连接蛋白，蛋白激酶α（PKCα）既是TLR4信号通路的下游分子，又是调控Occludin表达的主要蛋白。本项目组前期的研究已证实，TLR4调控的信号通路参与了DHCA脑损伤过程，观察到 Occludin表达下降，由此本项目组推测，PKCα介导了TLR4信号通路对Occludin的表达，引起BBB结构和功能破坏，最终导致脑损伤。本研究联合应用多种实验技术，通过大鼠DHCA模型和BMEC 氧-葡萄糖剥夺（OGD）模型分别进行体内和体外实验验证，试图从PKCα介导TLR4信号通路调控Occludin表达分子机制角度阐明DHCA脑损伤，为寻找新颖内源性保护调控靶向分子、开发新型DHCA神经保护策略提供理论依据。

Cerebral injury result from DHCA is an important factor influencing patient's prognosis.TLR4 signaling pathway involved ischemic reperfusion injury,and Occludin is the main protein consisting of tight juction in BBB from BMEC,while PKCα is a downstream molecular of TLR4 as well as rerulator of Occludin expression.Our pre-experiment results have confirmed TLR4 pathway participating DHCA cerebral injury and decrese of Occludin.We hypothesize PKCα mediates TLR4 regulating expression of Occludin,further result in cerebral injury.Combining multiple technology,we try to elucidate the pathogenesis of cerebral injury from the view molecular mechnism concerned of PKCα mediating TLR4 affecting the expression of Occludin.The aim of this study is to exploring the novel endogenous target molecular and provide theory evidence to develop novel neuroproctection strategy.