Decorin对急性缺血性卒中后血脑屏障中ZO-1蛋白的作用及机制研究

项目名称： Decorin对急性缺血性卒中后血脑屏障中ZO-1蛋白的作用及机制研究

项目编号： No.81501008

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 张磊

作者单位： 中国人民解放军第二军医大学

项目金额： 17.5万元

中文摘要： 急性缺血性卒中后血脑屏障的破坏是引起后续脑损伤的关键因素。蛋白聚糖Decorin（DCN）广泛存在于神经血管单元外基质中，但DCN在脑卒中过程中的作用机制还不清楚。前期动物实验中发现DCN在急性缺血大鼠血管组织中高表达；在急性缺血后0-3天内小鼠血清DCN表达升高，3-7天内血清DCN表达降低。脑微血管内皮细胞缺氧/复氧诱导实验提示DCN预处理能降低MMP-9的表达，减少缺氧损伤造成的紧密连接蛋白ZO-1的降解。已有研究证实MMP-9与急性缺血性卒中后紧密连接蛋白的破坏有关。我们推测DCN可能通过直接或者间接作用调控MMP-9及相关因子的表达对急性缺血性卒中后紧密连接蛋白ZO-1的破坏起到保护作用。本研究拟在已有的基础上，通过动物实验和细胞水平研究，研究脑卒中后DCN变化机制，及其对ZO-1影响及其相关信号通路，并通过调控DCN表达研究其与卒中预后的相关性，为缺血性脑卒中防止提供新的思路。

中文关键词： 缺血性脑卒中；血脑屏障；ZO-1；Decorin

英文摘要： Stroke is the leading cause of death and disability of adults in China, and the majority is ischemic. The blood-brain barrier disruption after acute ischemic stroke is the key factor for the subsequent brain damage. Decorin is a kind of proteoglycans existing profoundly in extracellular matrix of the central nervous system vasculature. In a previous study , in animal model, DCN highly expressed in the vascular struture of acute infarction. The serum decorin level was enhanced after being operated with middle cerebral artery occlusion in rats during 3 days after onset, and decreased from 3 days to 14 days. DCN can reduce the expression of MMP - 9 in the cerebral microvascular endothelial cell during the hypoxia/reoxygenation environment, meanwhile, it can reduce the degradation of ZO-1 due to the hypoxia damage.Latest research shows that MMP-9 was related to the tight junction proteins disruption after acute ischemic stroke. We speculated that DCN may play a direct or indirect role in regulating the expression of MMP-9 and protecting the degradation of ZO - 1.On this basis, to examine the function of decorin in ischemic stroke process, we planed to explore the changes and mechanism of DCN after stroke. We wanted to explore the effect of DCN to the ZO-1 and its related signal transduction pathways. Also we wanted to explore its correlation with the prognosis of stroke by regulating its expression. These researches will be helpful to provide new experimental basis and new targets for stroke therapy.

英文关键词： ischemic stroke;blood brain barrier;ZO-1;Decorin