项目名称: bFGF经FGFR1-c-SRC-Cav1信号级联促进创伤性脑损伤后血脑屏障恢复的机制研究
项目编号: No.81472165
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: 张宏宇
作者单位: 温州医科大学
项目金额: 61万元
中文摘要: 创伤性脑损伤后血脑屏障(blood brain barrier,BBB)的破坏是造成继发性脑损伤的重要原因。本课题组前期研究成果表明,外源性bFGF可以改善脑外伤后血脑屏障(BBB)及脑微血管内皮细胞紧密连接和通透性;诱导窖蛋白(Cav1)的表达;其机制可能通过调控RhoA/Rock以及Akt信号途径发挥保护作用。本项目通过构建创伤性脑外伤模型,研究bFGF改善和恢复BBB破坏的作用与FGFR1-c-SRC-Cav1-RhoA级联的关系;并利用RNA干扰和Cav1基因敲除小鼠明确Cav1在bFGF促进BBB恢复中的作用及其调控机制,观察下游信号RhoA/Rock变化;同时,在脑微血管内皮细胞水平上研究bFGF经FGFR1-c-SRC-Cav1-RhoA信号改善和修复BBB损伤的意义。旨在通过本项目研究,阐明bFGF促进创伤性脑损伤后BBB恢复和再生的分子机制。
中文关键词: 创伤性脑损伤;碱性成纤维细胞生长因子;窖蛋白;血脑屏障
英文摘要: Disruption of blood brain barrier (BBB) is the major cause of the continuous injury after traumatic brain injury. Our previous studies demonstrated that exogenous bFGF improved BBB, tight junction and adherision junction after traumatic brain injury, induced the expression of Cav1, the mechanism may involved in the regulation of RhoA/Rock and Akt pathways. In this project, we plan to construct the models of traumatic brain injury, investigate the functions of bFGF in the improvement and recovery of BBB and the relations to FGFR1-c-SRC-Cav1-RhoA cascades. RNA interference and Cav1 knockout mice will be performed, to confirm the role of Cav1 in the function of bFGF in BBB injury and the changes of downstream signals RhoA/Rock. Meanwhile, explore the role of bFGF repair and improve BBB via FGFR1-c-SRC-Cav1-RhoA signals in brain micro vascular endothelial cells. This study will demonstrates the mechanism of bFGF improves the recovery and regeneration of BBB after traumatic brain injury.
英文关键词: Traumatic brain injury;bFGF;caveolin;blood brain barrier