缺氧预适应对成年小鼠脑缺血损伤引起的系统性炎症反应的作用及分子机制

项目名称： 缺氧预适应对成年小鼠脑缺血损伤引起的系统性炎症反应的作用及分子机制

项目编号： No.81471332

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： 张雯婷

作者单位： 复旦大学

项目金额： 70万元

中文摘要： 脑卒中是我国发病率、致死率和致残率第一位的疾病。脑缺血不仅导致中枢神经元的损伤，而且会刺激外周免疫系统，引起脑组织继发性炎性损伤。抑制脑缺血引起的系统性炎症反应逐渐成为脑卒中的治疗靶点。缺氧预适应能够增加神经元对致死性损伤的耐受性，然而它在调节脑缺血损伤后外周免疫反应中的作用尚不清楚。我们证明了缺氧预适应对成年小鼠脑缺血/再灌注损伤的保护作用与抑制脾脏免疫细胞的动员、MMP-9的产生和M1小胶质细胞/巨噬细胞的激活有关。中枢细胞损伤释放的ATP通过作用于中性粒细胞和巨噬细胞上的P2X7受体导致其激活，引起炎症反应。本项目旨在阐明缺氧预适应是否是通过诱导炎症细胞HIF-1下游基因CD39或CD73的表达，促进ATP代谢生成腺苷，抑制M1巨噬细胞和中性粒细胞的激活，发挥神经保护作用的假说。

中文关键词： 脑保护；脑卒中；脑缺血再灌注损伤

英文摘要： Stroke is the leading cause of death in China.Cerebral ischemia not only induced the neuronal death in CNS, but also stimulate the systemic inflammatory response characterized with the release of immune cells from spleen,activation of peripheral neutrophils and macrophages as well as the production of cytokines.Suppress the systemic inflammatory response is a new strategy in the treatment of stroke. Hypoxic preconditioning protects neurons against lethal insult, however,its impact on the systemic inflammatory response following ischemia is still under investigation. Our previous research suggested that hypoxic preconditioning inhibited the releas of splenic cell after cerebral ischemia/reperfusion, the level of MMP-9 in circulation and the activation of M1 macrophages. ATP relased from the central nervous system stimulates the activation of neutrophil and macrophages via P2X7 receptor.Here, we hypothesis that hypoxic preconditioning promotes the expression of CD39 and CD73, which faciliate the systhesis of adenosine, and suppresses the systemic inflammatory response induced by cerebral ischemia.

英文关键词： Neuroprotection;Stroke;Cerebral ischemia and reperfusion