围心脏停搏期的远程缺血处理诱导大鼠内源性脑保护的实验研究

项目名称： 围心脏停搏期的远程缺血处理诱导大鼠内源性脑保护的实验研究

项目编号： No.81471831

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 朱水波

作者单位： 中国人民解放军中部战区总医院

项目金额： 72万元

中文摘要： 心肺复苏后脑损伤是心脏停搏（CA）患者复苏后综合症的主要表现之一，也是自主循环恢复后致死的主要原因。心肺复苏造成脑神经细胞的缺血再灌注损伤，继而导致线粒体通透性转换孔（mPTP）的开放是造成脑神经凋亡及脑损伤的主要机制。近年研究发现针对目标脏器进行的短暂肢体缺血预处理和后处理能诱导内源性脏器保护。我们在国内首先发现大鼠心肌缺血期肢体缺血处理也可诱导心肌保护，减少促凋亡蛋白表达，其作用机制与抑制心肌线粒体通透性转换孔(mPTP)的开放有关。本研究在我们前期工作基础上，提出利用围心脏停搏期的远程缺血处理，进行策略性的内源性脑保护的诱导，以达到抑制mPTP开放，减轻脑细胞凋亡，从而促进脑保护，减轻脑损伤。本研究拟采用窒息性大鼠CA/CPR模型，探讨围CA期肢体缺血处理与脑保护的关系，抗凋亡机制，并探求较适用的内源性脑保护策略。

中文关键词： 心肺脑复苏；脑损伤；心跳骤停；线粒体；细胞凋亡

英文摘要： Cerebral injury is one of the main performance of post cardiac arrest syndrome, and it is also the main cause of death of those patients who got a return of spontaneous circulation. Cardiopulmonary resuscitation promoted neuron ischemia/reperfusion injury, and the subsequent opening of cerebral cellular mitochondrial permeability transition pore(mPTP) is a main part of the mechanism of neuron apoptosis. Researches reported in recent years had verified that remote preconditioning or post-conditioning performed by transient limb ischemia aimed to an important organ could introduce an endogenous organic protection.We first reported in China that rats' limb ischemia during cardiac ischemia period (remote perconditioning) could introduce myocardial protection and decrease the expression of pro-apoptosis protein. The mechanism was related with inhibition the opening of mPTP. This subject, based upon our preliminary works, proposed a new cerebral protection strategy which should be performed by remote preconditioning, perconditioning or post-conditioning peri-cardiac arrest period. This strategy would promote brain protection by inhibition of the opening of mPTP and decreasing cellular apoptosis. The study is planned to use a choking rat's CA/CPR model to investigate the relationship between transient limb ischemia and cerebral protecion, the mechanism of anti-apoptosis. The ultimate aim is to seek a applicative cerebal protection stratege for those CA patients.

英文关键词： cardiopulmonary resuscitation;cerebral injury;cardiac arrest;mitochondrion;apoptosis