大鼠低血糖性脑水肿的分子机制研究

项目名称： 大鼠低血糖性脑水肿的分子机制研究

项目编号： No.31271125

项目类型： 面上项目

立项/批准年度： 2013

项目学科： 生物科学

项目作者： 赵玉武

作者单位： 上海交通大学

项目金额： 85万元

中文摘要： 血糖降低导致交感神经兴奋或中枢神经功能障碍称为低血糖症。低血糖较高血糖具有更迅速、直接且严重的危害；反复发作可导致永久性脑功能障碍及痴呆；急性低血糖可引起血脑屏障（BBB）损害及脑水肿，是低血糖性脑损伤的重要原因之一。但迄今为止，低血糖性脑水肿发生和发展的分子机制尚未阐明。我们前期研究表明AQP4和BBB紧密连接蛋白在低血糖性脑水肿中有重要的作用，结合文献学习及前期实验基础，我们提出"AQP4和紧密连接蛋白Occludin有着相互作用关系，在低血糖性脑水肿的发生中共同起作用"。基于此，本项目拟在共培养的SD大鼠大脑星形胶质细胞和脑微血管内皮细胞中证实AQP4和紧密连接蛋白Occludin的相互作用，并从体内和体外两个方面证实AQP4和Occludin在低血糖性脑水肿中的作用，进一步阐明大鼠低血糖性脑水肿的分子机制，为低血糖性脑水肿的早期防治提供新的思路和靶点，具有重要的理论价值及临床意义。

中文关键词： 低血糖；脑损伤；脑水肿；水通道蛋白4；血脑屏障

英文摘要： The decrease of blood glucose level resulting in sympathetic arousal or central nervous system dysfunction is called hypoglycemia, which has more severe immediate brain injury than hyperglycemia. Recurrent attacks of hypoglycemia can lead to mental decline and accelerated brain dementia.Acute hypoglycemia can cause cerebral edema, which often brings irreversible damage to blood brain barrier and is an important cause of hyperglycemic brain injury. As so far, the origin and development mechanism of hypoglycemic cerebral edema has not yet been fully elucidated. Our initial study found that aquaporin-4 and tight junction proteins played a very important role in hypoglycemic cerebral edema. Based on the reports from other labs and our own previous studies，we presumed that aquaporin-4 and occludin of tight junction proteins interact with each other during hypoglycemic cerebral edema. In this study, we plan to demonstrate the interactions between aquaporin-4 and occludin in cocultured astrocytes and brain microvascular endothelial cells of SD rats. We are determined to confirm the effects of the interaction between aquaporin-4 and occludin on hypoglycemic cerebral edema in vivo and in vitro, and explore the molecular mechanism of hypoglycemic cerebral edema. This study would provide a fundamental theory and practical

英文关键词： hypoglycemia；brain damage；brain edema；AQP4；Blood-brain barrier