Mir-21参与TSH调控巨噬细胞M1极化促进动脉粥样硬化的分子机制

项目名称： Mir-21参与TSH调控巨噬细胞M1极化促进动脉粥样硬化的分子机制

项目编号： No.81500595

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： 陈文斌

作者单位： 山东大学

项目金额： 18万元

中文摘要： 流行病学资料显示，TSH是动脉粥样硬化的独立危险因素。我们前期临床研究发现TSH水平与动脉粥样硬化斑块厚度呈正相关，而且亚临床甲减患者TSH与mir-21增加有关；TSH受体敲除小鼠高脂喂养后动脉粥样硬化斑块面积减少，缺少TSH受体的巨噬细胞在TSH处理后M1型极化减弱，然而至今国内外对此尚无报道。本项目由TSH切入,以促进动脉粥样硬化的巨噬细胞为主要研究对象，应用体内实验（在TSHR基因敲除小鼠，骨髓移植，体内RNA干扰等多种动物模型）和体外实验（TSH刺激巨噬细胞，基因沉默和过表达，染色质免疫共沉淀，荧光素酶报告基因等技术）相结合的方法，阐明TSH通过STAT3/mir-21/PTEN/NF-kB通路诱导巨噬细胞M1型极化的作用及分子机制，为揭示TSH在动脉粥样硬化发生发展中的作用提供新思路。

中文关键词： 促甲状腺激素释放激素；巨噬细胞；极化；动脉粥样硬化；小分子RNA

英文摘要： Epidemiology data shows that subclinical hypothyroidism was associated with atherosclerosis incidence. Our group have found that the TSH level was positively correlated with the plaque thickness ， mir-21 level was elevated in the serum from patients with subclinical hypothyroidism, the plaque area and M1 cytokines factors decreased in the TSHR knockout mice after high fat diet treatment, no research on the mechanism has been reported. This study takes TSH as the starting point, macrophage as the object of research, combines in vivo study(high fat diet treatment of TSHR gene knockout mice, bone marrow transplantation mice, in vivo RNA interference) and in vitro study(TSH treatment, gene overexpression and silence,CHIP,Luciferase Assay), tries to clarify the mechanisms of how TSH induces the M1 polariztion of macrophages via STAT3/mir-21/PTEN/NF-kB pathway and provides new insights into the roles of TSH plays in the incidence and progress of atherosclerosis.

英文关键词： TSH;macrophage;polarization;atherosclerosis;microRNA