Nrf2/HO-1信号通路抑制动脉粥样硬化中平滑肌源性泡沫细胞形成机制研究

项目名称： Nrf2/HO-1信号通路抑制动脉粥样硬化中平滑肌源性泡沫细胞形成机制研究

项目编号： No.81500356

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： 尹延伟

作者单位： 中国人民解放军第四军医大学

项目金额： 18万元

中文摘要： 泡沫细胞是构成动脉粥样斑块的主要成分，早期动脉粥样硬化病变中的泡沫细胞主要来源于巨噬细胞，而在中晚期动脉粥样硬化病变中血管平滑肌细胞成为泡沫细胞的主要来源。因此，积极研究抑制血管平滑肌源性泡沫细胞形成机制对防治动脉粥样硬化具有重要的现实意义。之前有研究证实Nrf2/HO-1信号通路在调控巨噬细胞泡沫化过程中发挥重要抑制作用，但至今尚无关于Nrf2/HO-1信号通路调控血管平滑肌细胞泡沫化研究。本课题拟在前期研究基础之上，从Nrf2/HO-1信号通路调节炎症反应及胆固醇酯胞内合成的角度，结合国内外最新研究进展，以Nrf2→HO-1—TLR4→炎症细胞因子（IL-1β, IL-6和TNF-α）→ACAT1的调控作用为切入点，对平滑肌源性泡沫细胞形成的分子机制进行深入探讨。该项目有充分的立论依据及前期实验基础，将进一步揭示血管平滑肌细胞泡沫化机制，为动脉粥样硬化防治提供新的靶点和干预路径。

中文关键词： 动脉粥样硬化；血管平滑肌细胞；泡沫细胞

英文摘要： Foam cells are the key components of atherosclerotic plaque. Previous studies have demonstrated that foam cells in early-stage atherosclerotic lesions are derived mainly from macrophages. However, in mid- and late-stage atherosclerosis, vascular smooth muscle cells become the main source of foam cells. Therefore, it is very important to investigate the mechanisms of inhibiting vascular smooth muscle-derived foam cells formation. Previous studies have indicated that Nrf2/HO-1 signaling pathway play inhibitory roles in macrophages-derived foam cells formation, but so far there have not been any studies regarding the association between Nrf2/HO-1 signaling pathway and vascular smooth muscle-derived foam cells. Based on preliminary research results, we intend to further investigate the molecular mechanism of vascular smooth muscle-derived foam cells formation from the view of inhibition of inflammation response and intracellular cholesterol ester synthesis. Briefly，the purpose of this study was to investigate whether Nrf2/HO-1 signaling pathway inhibits vascular smooth muscle-derived foam cells formation via affecting the following signal path: Nrf2→HO-1—TLR4→Cytokines（IL-1β, IL-6 and TNF-a）→ACAT1. There are sufficient evidence and preliminary research results supporting the present study. Our study could further uncover the mechanism of vascular smooth muscle-derived foam cells formation. Meanwhile, it will also present new target and avenue for prevention and therapy of atherosclerosis.

英文关键词： atherosclerosis;vascular smooth muscle cell;foam cell