调控巨噬细胞极化的microRNA分子鉴定及其在CVB3诱导的急性病毒性心肌炎中的作用

项目名称： 调控巨噬细胞极化的microRNA分子鉴定及其在CVB3诱导的急性病毒性心肌炎中的作用

项目编号： No.81472017

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： 吕坤

作者单位： 皖南医学院

项目金额： 80万元

中文摘要： 研究发现，病毒性心肌炎时心肌细胞损伤与巨噬细胞浸润有关，不同极化状态的巨噬细胞在病毒性心肌炎发病过程中发挥重要作用。然而，调控巨噬细胞极化的机制尚不清楚。申请人前期发现，体外极化的巨噬细胞miRNA表达谱存在差异；进一步研究发现，CVB3感染的雌、雄小鼠心脏浸润巨噬细胞（M2/M1）分别高表达miR-125b和miR-155，提示上述两个miRNAs参与了M1/M2极化过程,然而其机制不明。本研究中，我们拟比较分析体内外不同极化状态的巨噬细胞miRNA表达谱的变化，从而筛选出调控巨噬细胞极化的个体miRNA；通过生物信息学预测和报告载体实验鉴定其靶基因；通过阻断或过表达等方法，体内外观察个体miRNA调节靶基因表达和功能对巨噬细胞极化的影响及其在病毒性心肌炎发病过程中的作用，从而为病毒性心肌炎的发病机制研究和生物学防治提供新的理论基础和实验依据。

中文关键词： 巨噬细胞；极化；微小RNA；CVB3

英文摘要： Viral myocarditis (VMC) is a kind of clinical common infectious disease of cardiovascular system. Accumulating documents indicated that cardiac injury was associated with heart-infiltrating macrophages and differentially polarizated macrophages played a role in VMC. However, mechanisms that underlie macrophage polarization remain largely undefined. MicroRNAs are short inhibitory non-coding RNAs that block the translation and play important biological roles in cell development, differentiation and immune regulation. Our preliminary experiments found that differentially expressed microRNA profiles existed in polarizated macrophages in vitro, indicating that individual microRNA may play a role in macrophage polarization. The differential expression of selected miRNAs was validated by real-time qRT-PCR: miR-155-5p was upregulated and miR-125-5p was downregulated in heart infiltrated macrophages from CVB3 infected male and female mice, respectively. In the present study, we aim to screen individual microRNAs associated with macrophage polarization by comparative analysis of microRNAs profiles in polarized macrophages. Besides, we will explore the possible mechanisms of individual microRNAs in regulating macrophage polarization and its potential role in VMC. Meanwhile, we will identify mRNA targets binding to individual microRNA. Our study will help to further understand the mechanism of VMC and provide a novel therapeutic strategy in treating inflammatory cardiac disease.

英文关键词： macrophage;polarization;microRNA;CVB3