无创性低温再灌注对心肺复苏后脑损伤的早期保护作用及其线粒体机制

项目名称： 无创性低温再灌注对心肺复苏后脑损伤的早期保护作用及其线粒体机制

项目编号： No.81471834

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： 管军

作者单位： 中国人民解放军第二军医大学

项目金额： 72万元

中文摘要： 现有低温方法对心肺复苏后脑损伤有明确脑保护作用，但明显滞后于脑再灌注损伤早期进程并错过早期治疗窗口，特别是活性氧簇爆发产生和线粒体通透性转换孔（mPTP）持续开放。我们提出低温再灌注方法抑制复苏后早期氧化应激反应保护脑功能的新思路。颈部因解剖位置独特而成为无创方法降低脑温最高效的体表部位。我们设计并验证了颈部快速致冷，在心脏复跳前充分预冷进入脑组织的血液，在心脏复跳后对脑组织进行低温再灌注并迅速降低脑温的治疗方法。本项目拟采用兔室颤心肺复苏模型，采用电子自旋共振、激光共聚焦显微镜、Westen Blot等技术，研究低温再灌注能否改善心脏复跳后早期线粒体呼吸功能，抑制活性氧爆发产生并阻止mPTP持续开放。研究在阻断剂阻断PI3K/Akt/GSK-3β通路后，低温再灌注是否仍能有效抑制mPTP持续开放。本研究将开发出适用于现场急救的能抓住复苏后脑损伤早期治疗窗口的低温脑保护措施并阐明其机制。

中文关键词： 心肺脑复苏；脑损伤；线粒体；亚低温

英文摘要： Despite of its proved cerebral protective effects, current therapeutic hypothermia which is initiated after return of spontaneous circulation (ROSC) significantly lag behind the early process of cerebral reperfusion injury and may miss the optimal treatment window，reactive oxygen species burst production and continous opening of mPTP. In this study, we put forward the hypothesis that cerebral cool reperfusion protect the brain function by inhibiting oxidative stress. Our preliminary experiments showed that rapid neck cooling started at the beginning of CPR may pre-cool the temperature of blood in neck area including carotid vessels toward brain before ROSC in a rabbit model of ventricular fibrillation. The brain is cool reperfused immediately after return of spontaneous circulation and rapidly reach the target temperature of hypothermia. We will investigate whether this innovative cool reperfusion strategy will improve ultrastructure pathology of brain in post-cardiac arrest animals. We will also investigate the changes of mitochondrial energy storage, respiratory function, and production of reactive oxygen species in the early stage after ROSC. Finally, we will investigate whether the beneficial effects of cool reperfusion strategy are attributed to the modulation of PI3K/Akt/GSK-3β/mPTP signal pathway. We will develop an innovative hypothermic treatment, which may both capture the early treatment opportunity of post-cardiac arrest cerebral injury and be of high clinical applicability, and elucidate its mitochondrial mechanisms。

英文关键词： Cardiopulmonary Cerebral Resuscitation;Cerebral Injury;Mitochondria;mild hypothermia