miR-22靶向调控CBP基因对缺血再灌注心肌的多重保护作用及机制研究

项目名称： miR-22靶向调控CBP基因对缺血再灌注心肌的多重保护作用及机制研究

项目编号： No.81200088

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 医学一处

项目作者： 杨简

作者单位： 三峡大学

项目金额： 23万元

中文摘要： 心肌缺血再灌注损伤(IRI)是影响冠心病再灌注治疗效果的重要因素，然而目前各种防治措施对心肌的保护作用有限，其原因与干预靶点的作用单一性有关。CREB结合蛋白(CBP)作为众多信号转导途径的共同调节子，可参与多基因改变介导的心肌IRI。本课题组前期研究发现，CBP基因沉默可通过抗炎、抗细胞凋亡对再灌注心肌发挥保护作用。最新研究表明，再灌注心肌中有数十种表达差异的miRNA，其中miR-22表达明显下调。生物信息学方法预测miR-22与CBP mRNA3'-UTR存在关键结合位点，提示miR-22可靶向调控CBP基因发挥心肌保护。但作用方式与调控机制如何？均未见报道。本项目拟以"现象描述-整体作用-分子机制"的思路为指导，观察过表达和沉默miR-22对心肌IRI的影响，并深入探讨miR-22靶向调控CBP基因对再灌注心肌的多重保护作用及信号分子机制，为开辟新的心肌IRI防治途径奠定理论基础。

中文关键词： 微小RNA；CREB结合蛋白；炎症；细胞凋亡；心肌缺血再灌注损伤

英文摘要： Myocardial ischemia reperfusion injury (IRI) is an important factor in reducing the clinical effects of reperfusion therapy for coronary heart disease. However, a variety of preventive measures at present have a limited cardioprotective effect, which may be ascribed to the unitary role of intervention targets. CREB binding protein (CBP) as a common regulator of numerous signal transduction pathways, is involved in the regulation of myocardial IRI. Previous work from our laboratory has demonstrated that CBP gene silencing could potently attenuate myocardial IRI through its anti-inflammation and anti-apoptosis effects. The latest study has shown that there are dozens of miRNAs differentially expressed in the ischemia reperfusion myocardium. Among such miRNAs, miR-22 was found to be highly down-regulated. Furthermore, the software TargetScan predicts that the 3'-UTR of CBP mRNA contains critical target sites for miR-22, suggesting miR-22 may confer cardioprotection via the targeted regulation of CBP. Nevertheless, the exact regulatory mechanism is still not elucidated so far. In the present study, we attempt to use the idea of "phenomenon description-overall effect-molecular mechanism", to observe the influence of miR-22 overexpression or silencing on myocardial IRI and explore the multiple protective effect and mo

英文关键词： miRNA；CBP；inflammation；apoptosis；myocardial ischemia reperfusion injury