基于TLR4/MyD88/NF-κB信号通路、miRNA-146a表达探讨补肾方药抗动脉粥样硬化的效应机制

项目名称： 基于TLR4/MyD88/NF-κB信号通路、miRNA-146a表达探讨补肾方药抗动脉粥样硬化的效应机制

项目编号： No.81202731

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 医学八处

项目作者： 申定珠

作者单位： 上海中医药大学

项目金额： 23万元

中文摘要： 动脉粥样硬化（AS）及其引起的心脑血管疾病是目前主要致死性疾病，发病机制尚不明确。研究表明miRNA-146可负向调控与AS关系密切的TLR4/MyD88/NF-κB通路。本项目前期研究证实补肾方药疗效肯定，拟采用ApoE-/-小鼠复制AS模型，结合Real time PCR、Western blot、差异蛋白质组学等技术，观察TLR4、MyD88、IRAK、TRAF6、NF-κBp65、miRNA-146a、MCP-1、TNF-α、ICAM-1的变化及补肾方药的干预作用，构建miRNA-146a与TLR4/MyD88/NF-κB通路靶蛋白相互作用网络。拟证实：调控TLR4/MyD88/NF-κB通路中关键因子的表达可能是补肾方药抗AS的重要机制，补肾方药可能通过干预miRNA-146a表达反馈调控TLR4/MyD88/NF-κB通路，为从补肾治疗AS相关疾病提供多层次、多靶点的科学依据。

中文关键词： 动脉粥样硬化；TLR4/MyD88/NF-κB通路；差异蛋白质组学；miRNA-146a；补肾中药复方

英文摘要： Atherosclerosis (AS) and induced Cardio-cerebral vascular diseases are the main fatal diseases, and the etiological factor and pathogenesis are not clear. It is demonstrated that TLR4/MyD88/NF-κB signal transduction pathway has a close relationship with AS, and miRNA-146a can regulate the pathway negatively. Earlier research of ours have demonstrated that the curative effect of Shen invigorating compounds Shoushen groule definited. On the basis of preliminary study, AS animal model will be maked by ApoE-/- mice in the project, methods of Real time PCR,Western blot and differential proteomics will be used. Expression of TLR4, MyD88, IRAK, TRAF6, NF-κBp65, miRNA-146a, MCP-1, TNF-α and ICAM-1 will be detected and that intervention of Shen invigorating compounds, and building network interactivity of miRNA-146a and proteins of TLR4/MyD88/NF-κB pathway. To be confirmed: Regulation the expression of key factors of TLR4/MyD88/NF-κB signal transduction pathway maybe the main mechanism of Shen inviorating compounds on AS, and Shen inviorating compounds maybe regulate TLR4/MyD88/NF-κB signal transduction pathway through intervention expression of miRNA-146a negative feedback. All that for prividing the multi-level and multi-target scitific evidence for curing AS related diseases.

英文关键词： Atherosclerosis；TLR4/MyD88/NF-κB pathway；Differential proteomics；miRNA-146a；Shen invigorating compounds