模拟失重通过p53/AMPK/mTOR通路诱导自噬调节血管内皮细胞功能

项目名称： 模拟失重通过p53/AMPK/mTOR通路诱导自噬调节血管内皮细胞功能

项目编号： No.81471817

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： 孙喜庆

作者单位： 中国人民解放军第四军医大学

项目金额： 75万元

中文摘要： 失重导致的心血管功能失调是长期航天飞行中危害航天员健康的重要问题之一，其发生涉及多重复杂机制，文献和我们前期研究工作表明，血管内皮细胞功能异常在失重致心血管功能失调中发挥重要作用。我们最近研究发现，模拟失重可引起血管内皮细胞自噬增强，p53表达增高，而自噬的激活与血管内皮细胞功能密切相关，提示失重可能通过激活p53及其下游分子诱导细胞自噬调控血管内皮细胞功能。本课题拟在此基础上，采用回转器模拟失重培养血管内皮细胞、尾悬吊复制大鼠失重模型，从细胞和整体动物水平证实自噬在失重致血管内皮细胞功能异常中的作用，进一步明确p53/AMPK/mTOR交互作用在失重条件下血管内皮细胞自噬激活中的调控机制。本研究将有助于深化对失重致心血管功能失调机制的认识，为失重致航天员心血管功能失调的防护提供新的思路和理论指导，具有重要的理论和实际意义。

中文关键词： 模拟失重；自噬；p53；mTOR；血管内皮细胞

英文摘要： Cardiovascular deconditioning induced by weightlessness can adversely affect the health of astronaut, lower performance of physical work and endanger the safety of spaceflight. However, the underlying mechanisms are multifactorial and remain to be fully elucidated. Literatures and our previous data showed that changes of endothelial cells resulted in alteration of vascular function induced by micrograty. Our recent works showed that simulated microgravity activated autophagy of vascular endothelial cells and increased p53 expression. Evidences indicated that the activation of autophagy plays imptortant roles in regulating endothelial cells functions. Therefore, we speculate that simulated microgravity regulates endothelial cells function by p53/AMPK/mTOR activating autophagy. In this study, we employ the clinostat and tail-suspended rats to simulate microgravity. Based on our previous studies, we explore the changes of autophagy in vitro and in vivo induced by simulated microgravity, and investigate the roles of autophagy activation in alterations of endothelial cells functions induced by simulated microgravity. We further investigate the role of p53/AMPK/mTOR in regulation of autophagy activation by simulated microgravity in endothelial cells. Our finding might help to know the possible mechanism of the cardiovascular dysfunctions induced by microgravity and provide some theoretical basis to the protection of postflight orthostatic intolerance.

英文关键词： simulated microgravity;autophagy;p53;mTOR;endothelial cell