针刺干预内质网应激调节脑缺血再灌注大鼠神经细胞自噬的分子机制研究

项目名称： 针刺干预内质网应激调节脑缺血再灌注大鼠神经细胞自噬的分子机制研究

项目编号： No.81202759

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 医学八处

项目作者： 舒适

作者单位： 中国人民解放军第二军医大学

项目金额： 23万元

中文摘要： 脑缺血再灌注损伤直接影响脑血管病的预后转归，如何积极减轻脑缺血再灌注损伤是防治脑缺血性疾病的关键。新近研究表明，自噬作为新的程序性细胞死亡方式，在细胞"存活"与"毁灭"切换中的意义重大。而内质网应激中非折叠蛋白质反应(UPR)是诱导细胞自噬的重要信号通路。基于这一新的科学发现，以及课题组前期有关针刺治疗脑缺血的临床与实验室研究证据，本项目拟采用大脑中动脉栓塞局灶性缺血再灌注大鼠模型，运用实时荧光定量PCR、western blot、RNA干扰等技术，通过动态观察针刺水沟穴对脑缺血再灌注损伤后内质网应激UPR信号转导通路诱导自噬的影响，从内质网应激UPR三条信号转导通路PERK/elF2α、Ire1/TRAF2、ATF6α的分子作用途径深入阐释脑缺血再灌注损伤后自噬的作用机制以及针刺水沟穴减轻脑缺血再灌注损伤可能物质基础与有效作用靶点，为针刺治疗脑缺血的临床应用提供实验与理论依据。

中文关键词： 脑缺血再灌注；针刺；自噬；内质网应激；非折叠蛋白质反应

英文摘要： Cerebral ischemia reperfusion injury directly affects the prognosis of cerebrovascular disease,so how to actively reduce cerebral ischemia and reperfusion injury is the key piont in preventing and treating cerebral ischemia disease.New research shows that autophagy as new programmed cell death way,plays an important role in the switch of "live" and "destroy" in cells. Meanwhile Unfolded protein response(UPR) responsed in endoplasmic reticulum stress(ERS) is an important signalling pathway to induce cells autophagy.Based on this new scientific discovery, and the clinical and experimental evidence in our earlier researches on treating cerebral ischemia by acupuncture, the project is using middle cerebral artery occlusion/reperfusion(MCAO/R) rat models and techniques of real-time fluorescent quantitative PCR(FQ-PCR), western blot and RNAi. The effect of UPR signalling pathways regulating autophagy by needling Shuigou(DU 26) after cerebral ischemia and reperfusion injury would be dynamically observed.From the molecule function way of three signal transduction pathways PERK/elF2α, Ire1/TRAF2, ATF6α of UPR, the mechanism of autophagy,material base and effective acting targets by needling Shuigou(DU 26) after cerebral ischemia reperfusion injury would be further explained. It can provide experimental and theoretical

英文关键词： Cerebral ischemia reperfusion；Acupuncture；Autophage；Endoplasmic reticulum stress(ERS)；Unfolded protein response(UPR)