脂联素干预ROS/RNS生成对心肺复苏后脑损伤的影响及其机制研究

项目名称： 脂联素干预ROS/RNS生成对心肺复苏后脑损伤的影响及其机制研究

项目编号： No.81471836

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： 曹钰

作者单位： 四川大学

项目金额： 72万元

中文摘要： 心肺复苏后脑损伤是由脑组织缺血缺氧导致大量自由基生成、进而诱发一系列反应所致，其致残致死率极高，但目前尚无有效的治疗手段减轻此损伤。本课题组前期研究发现，在强氧化剂攻击的情况下，脂联素（Adiponectin, APN）能保护脑、肺、心、肝功能，但具体机制尚不明确。研究提示，APN可能是通过减轻脑组织内的急性氧化/硝化应激损伤以及抑制脑组织内炎症反应而实现其脑保护作用，因此，本项目拟通过建立缺氧无糖/复氧有糖的缺血缺氧再灌注细胞模型和APN基因敲除C57/6L小鼠心肺复苏模型，深入研究脂联素干预心肺复苏后，PKA-ATP-ROS/RNS信号通路、炎性介质介导的脑组织细胞损伤变化情况，明确APN干预ROS/RNS和炎性介质生成对心肺复苏后脑组织损伤的保护作用及机制。本项目为心肺复苏患者脑损伤的发病机制及制定相应诊疗方案提供理论依据，对延长心肺复苏患者的存活时间、改善其生存具有重要意义

中文关键词： 心肺复苏；脑损伤；脂联素

英文摘要： The post-cardiac arrestbraininjury can be caused by oxidative stress which means excessive free radicals production and accumulationin brain duringischemia and reperfusion. It accounts for high mortality which is in part due to the lack ofeffectivetherapies.Adiponectinis a recently identified proteinthat is predominantly, but not exclusively, expressedby the adipose tissue.Our previous works revealed that adiponectin can protect the functions of brain,lung,heart and liver under oxidative stress.but the exact mechanismis still underinvestigation.Recent research has indicated that the adiponectin receptor 1 and 2 can be expressed by neuronal cells. These findings provide the possibility that adiponectin may be used to decrease the Reactive Oxygen Species/Reactive Nitrogen Species and improve the brain injury following the cardiac arrest reperfusion.The study was designed to establish of ischemia-reperfusion cell model and adiponectin gene knockout C54BL/6J mice cardiac arrest model,and determine the effect of adiponectin on cardiac arrest-induced oxidative brain stress and explore the underlying mechanism.We hope to find a new point of view to improve the brain function and long-term survival rate of patients recovered from cardiac arrest.

英文关键词： Cardiopulmonary resuscitation;brain injury;adiponectin