蛛网膜下腔出血后脑微循环变化及调控机制的实验研究

项目名称： 蛛网膜下腔出血后脑微循环变化及调控机制的实验研究

项目编号： No.81471179

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： 宋锦宁

作者单位： 西安交通大学

项目金额： 70万元

中文摘要： 脑微循环改变是SAH后最重要的病理变化之一，胆碱能抗炎通路与脑皮层传播抑制是调控脑血管功能状态的重要环节。由于脑微循环变化及调控机制尚不清楚，目前缺乏对其有效的早期干预手段。本研究的主要目的在于揭示胆碱能抗炎通路在引起脑微循环血流障碍的作用，以及Ach和脑皮层传播抑制对其的影响和分子调控机制。我们将以免疫炎症和脑细胞膜功能相互作用为中心，以Ach和脑皮层传播抑制为突破点，运用放射性核素脑显像、新型细胞乏氧显像剂EF5/ELK3-51免疫组化、激光多普勒血流仪动态监测皮质血流、分子及细胞生物学和免疫荧光等技术，在分子、细胞、功能以及动物模型等水平上，综合研究脑微循环血流及脑乏氧代谢动态变化规律。我们重点研究炎性因子和SOCS-3改变及其分子机制，以及线粒体膜电位及皮层传播抑制对脑微循环血流的影响。以期阐明SAH后脑微循环变化规律及调控机制，为SAH的早期预警与干预提供理重要的理论及实验依据。

中文关键词： 蛛网膜下腔出血；脑微循环；免疫炎症；脑皮层传播抑制；调控机制

英文摘要： Cerebral microcirculation change after subarachnoid hemorrhage (SAH) is one of the most important pathologic changes, cholinergic anti-inflammatory pathway and cortical spreading depression (CSD) are the two key factors in regulating cerebrovascular function. Since the detail mechanism of the alteration and regulation of cerebral microcirculation change is still unclear, there lacks efficient interfere means in the early stage of the disease. The aim of current study is to explore the role of cholinergic anti-inflammatory pathway in causing disturbance of cerebral microcirculation flow and the affects of Ach and CSD and the underline mechanism. Our study will specifically target to the interaction of immune inflammation and brain cell membrane function, and will be established in the Ach and CSD as the breakthrough point. Utilizing the tools of radionuclide brain imaging, immunohistochemistry with EF5/ELK3-51 a new cellular hypoxia imaging agent, laser Doppler flowmetry, molecular biology and cell biology, we will the comprehensively dissect the mechanism of endothelial dysfunction from molecular and cellular levels to animal in vivo levels. We will focus on the change of function and underline mechanism of inflammatory factor and SOCS-3, including the effects of mitochondrial membrane potential and CSD on cerebral microcirculation flow. We expect to elucidate the change rules and regulation mechanisms of cerebral microcirculation after SAH, which will provide important novel clues in the prevention and treatment of SAH.

英文关键词： subarachnoid haemorrhage;cerebral microcirculation;immune inflammation;cortical spreading depression;regulation mechanisms