冠心病心外膜脂肪组织中差异性microRNAs调控apM1基因表达及其机制研究

项目名称： 冠心病心外膜脂肪组织中差异性microRNAs调控apM1基因表达及其机制研究

项目编号： No.81460059

项目类型： 地区科学基金项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 魏育涛

作者单位： 石河子大学

项目金额： 47万元

中文摘要： 心外膜脂肪(EAT)、脂联素（APN）与冠心病发生发展密切相关，冠心病患者EAT 中APN减少，其确切机制不明。MicroRNAs(miRNAs)通过转录后靶向mRNA调节人体超过1/3的编码蛋白质，可能对EAT中APN表达发挥重要作用，但目前二者之间关系及调控机制研究甚少。我们提出假说：冠心病EAT中存在差异性miRNAs，调控apM1(apM1特异性表达产物为APN)，影响APN表达，对冠心病进程产生影响。本研究以SD大鼠为研究对象，应用miRNAs芯片、生物信息学、基因过表达及抑制、RT-PCR、western-blot、FRET能量转移技术等分子生物学技术，通过体内、体外两部分实验，应用上调和抑制miRNAs来分析验证其对apM1表达的调控作用，旨在明确apM1在冠心病 EAT中表达调控的重要途径，为研究冠心病发病机制提供新思路，为寻找治疗干预的新靶点提供实验依据。

中文关键词： 动脉粥样硬化；脂联素；微小RNA；冠心病

英文摘要： Epicardial adipose tissue (EAT) and adiponectin(APN) are closely related to the initial and development of coronary atherosclerotic heart disease (CAD). Decreased APN was observed in EAT with CAD patients, but the mechanism has not been elaborated. MicroRNA(miRNA) are endogenous approximately 23 nucleotide noncoding RNA molecules that play important gene-regulatory roles in diverse regulation pathways and regulates the expression of approximately 30% of human protein-coding mRNAs at post-transcriptional level. MiRNAs likely play a key role in the regulation of APN expression, special production of apM1 gene, with unclear mechanism. We hypothesized that distinctive dysregulation miRNAs in EAT with CAD involved in coronary atherosclerosis process through regulated apM1 gene expression followed by our former research as well as EAT pathophysiology coupled with molecular mechanism of miRNAs. In this study, we used CAD SD rats model as well as adipose cell to study the apM1 gene expression and reason for decreased APN by distinctive miRNAs through microarray, real time PCR, gene transfection, western-blot, ELISA and fluorescence resonance energy transfer(FRET) etc. in vivo and in vitro, and furnished new idea plus novel target for intervening coronary atherosclerosis.

英文关键词： atheroscleosis;adiponectin;microRNAs;coronary atherosclerotic heart disease(CAD)