水通道蛋白参与脑损伤的机制和功能研究

项目名称： 水通道蛋白参与脑损伤的机制和功能研究

项目编号： No.81471253

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： 于常海

作者单位： 北京大学

项目金额： 80万元

中文摘要： 水是生理病理过程中极为重要的物质。水通道（water channels, aquaporins, AQPs）主要参与水的转运。脑中的AQPs也参与调控胶质细胞和神经元，进而参与众多生命过程，特别是损伤过程。目前，有很多对水通道功能和机制的研究表明水通道在不同生理病理状态下其各自表达和定位都有明显差异。因此，系统并深入地对不同水通道（AQP1, 3, 4, 5, 8, 9）在细胞水平调节水的通透性的功能和机制的研究成为热点课题。本项目试图通过本实验室成熟的划伤、缺血缺氧和兴奋性损伤模型，通过星形胶质细胞和神经元对比研究，深入了解不同水通道在脑损伤和修复过程中各自发挥的作用，并通过潜在的信号通路(MAPKs)和与离子通道（NKCC、Na, K-ATPase）的相互作用，阐明其分子机制，为水通道参与脑生理病理过程提供最基础的理论依据。

中文关键词： 创伤性脑损伤；星形胶质细胞；脑缺血；脑损伤；兴奋性毒性

英文摘要： Water is extremely important during physiological and pathological processes in the brain. Aquaporins (AQPs), membrane water channels, regulate neuronal and glial cells mainly through water transport, and thus participate in many life processes, especially during brain damage and disease. Currently, many studies on the functions and mechanisms of AQPs indicate that there are significant differences in their expression and localization during different physiological and pathological states. Therefore, studies on the regulation of the water permeability and mechanisms of different channels (AQP1, 3, 4, 5, 8 and 9), has become a hot topic. This project will allow an in-depth understand of the roles of different AQPs during brain damage and repair processes by studying them with a scratch model, an ischemic injury model and an exitotoxicity model. We plan to invevstigate the interaction between potential signaling pathways (MAPKs), ion channels (NKCC, Na+/K+-ATPase) and AQPs, to clarify the molecular mechanisms and provide a basic theoretical understanding.

英文关键词： traumatic brain injury;astrocyte;cerebral ischemia;cerebral injury;excitatory toxicity