内质网应激通过JAZF1/AKT/mTOR信号途径调控巨噬细胞自噬影响易损斑块的作用研究

项目名称： 内质网应激通过JAZF1/AKT/mTOR信号途径调控巨噬细胞自噬影响易损斑块的作用研究

项目编号： No.81501199

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： 王葱

作者单位： 重庆医科大学

项目金额： 17.5万元

中文摘要： 内质网应激和自噬是影响动脉粥样硬化（AS）易损斑块的重要因素，但目前对其影响AS易损斑块的作用机制尚不明确。.前期结果提示内质网应激极可能经JAZF1/AKT/mTOR信号途径调控巨噬细胞自噬而影响AS易损斑块。课题组在国家自然基金的资助下发现JAZF1基因过表达小鼠的糖脂代谢紊乱及AS病变均得到改善。我们拟在此基础上：进一步证实内质网应激时JAZF1/AKT/mTOR 途径在巨噬细胞中的存在；细胞实验分析内质网应激通过JAZF1/AKT/mTOR途径对巨噬细胞自噬的调控作用；动物实验分析内质网应激介导JAZF1/AKT/mTOR 途径对斑块内巨噬细胞自噬及AS易损斑块的调控作用；最后解析内质网应激通过JAZF1/AKT/mTOR途径调控巨噬细胞自噬的分子机制，重点关注其影响NF-κB途径，并利用抗体芯片及基因芯片寻找更多与JAZF1/AKT/mTOR途径调控巨噬细胞自噬相关的信号分子。

中文关键词： 内质网应激；JAZF1；巨噬细胞自噬；易损斑块

英文摘要： Endoplasmic reticulum stress and autophagy played an important role in the occurrence and development of unstable plaque of atherosclerosis. However, the mechanism is not clear. . Relative studies revealed that endoplasmic reticulum stress is impossible to regulate macrophage autophagy and unstable plaque of atherosclerosis via JAZF1/AKT/mTOR pathway. We found that JAZF1 overexpression improved glucose-lipid metabolism disorder and atherosclerosis. However, the molecular mechanism through which JAZF1/AKT/mTOR pathway regulates macrophage autophagy and unstable plaque of atherosclerosis is still largely unknown and warrants extensive studies. For this purpose/Therefore, we used endoplasmic reticulum stress activator to further validate the existence of JAZF1/AKT/mTOR pathway in macrophages. Moreover, using in vitro cell experiments in vivo animal experiment, the exact role of JAZF1/AKT/mTOR pathway under endoplasmic reticulum stress on regulating autophagy of macrophages was intensively analyzed.Subsequently, using in vivo animal experiment, we will explore JAZF1/AKT/mTOR pathway in autophagy and unstable plaque of atherosclerosis within endoplasmic reticulum stress. Finally, the mechanism of JAZF1 will be illuminated in macrophage autophagy through the interactions of NF-κB pathway. Nevertheless, AKT phosphorylation antibody array and AKT/mTOR signal pathway microarray were used to identify new moleculars involved in JAZF1/AKT/mTOR pathway-regulated autophagy of macrophage. This will provide new experiment and theoretical data for the mechanism of atherosclerosis.

英文关键词： Endoplasmic reticulum stress;JAZF1;Macrophage autophagy;Unstable plaque