基于脂筏调节血脑屏障紧密连接的扶正护脑法治疗脑卒中的分子机制研究

项目名称： 基于脂筏调节血脑屏障紧密连接的扶正护脑法治疗脑卒中的分子机制研究

项目编号： No.81202832

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： 刘元

作者单位： 北京中医药大学

项目金额： 24万元

中文摘要： 血脑屏障（BBB）通透性调节的中心环节是内皮细胞的紧密连接（TJ），TJ结构蛋白表达水平的变化与脑微血管通透性的改变及脑水肿的程度密切相关。脂筏是高流动性的细胞膜脂质双层内含胆固醇的特殊脂质和蛋白质的动态微区，它参与细胞蛋白转运。BBB上有大量的脂筏存在，TJ蛋白分布于脂筏中，其功能受胆固醇调节。BBB破坏是缺血性脑卒中急性期发生脑水肿及神经元毒性损害的核心病理过程之一，目前尚无特效保护方法。 以扶正护脑法作为脑卒中急性期的基础治疗方法在减轻脑水肿、保护神经元方面显示了较好的临床疗效。本研究旨在阐明以扶正护脑法作为脑卒中急性期基础治疗，保护血脑屏障的分子机制。通过分析参麦注射液干预后，TJ蛋白在脂筏区表达量的改变、位置分布的变化和结构功能的异常，对脑微血管内皮细胞间TJ功能的调控特性，探索扶正护脑方药治疗脑卒中的分子机制，为脑保护研究提供新的药物靶点。

中文关键词： 脂筏；紧密连接；血脑屏障；扶正护脑法；缺血性脑卒中

英文摘要： The central link in the regulation of blood-brain barrier (BBB) permeability is the tight junctions (TJ) between the endothelial cells. The change of the expression of TJ structural proteins is closely related to the extent of cerebral microvascular permeability and brain edema. Physically distinct, cholesterol- and sphingolipid-enriched dynamic micro-regions of the plasma membrane, known as "lipid rafts", are increasingly being recognized as important sites of protein and lipid trafficking and signal transduction. BBB is rich in lipid rafts. TJ proteins are believed to be incorporated within lipid rafts and TJ function is modulated by cholesterol. BBB destruction is one of the core pathological processes of brain edema and toxic damage to neurons in the acute phase of ischemic stroke, but there are no effective protective methods. Fu Zheng Hu Nao as the basic treatment of alleviating cerebral edema and protecting neurons in acute stoke has shown a better clinical efficacy. This study aims to clarify the molecular mechanisms of protecting BBB on the acute stroke treatment with Fu Zheng Hu Nao. Through the analysis of changes of TJ proteins expression, distribution and structure in lipid rafts after Shenmai injection treatment, explore the molecular mechanisms of Fu Zheng Hu Nao after acute stoke and provide a ne

英文关键词： lipid raft；tight junction；blood-brain barrier；Fu Zheng Hu Nao Treatment；ischemic stroke