RNase L在心肌缺氧缺血中的作用机制研究

reported. Our pre-project study for the first time has found that RNase L expression is decreased after cardiomyocyte hypoxia, we speculate that the reduction of RNase L participates in hypoxia-induced cardiomyocyte apoptosis, and this could be a new mechanism of cardiomyocyte adaptation to hypoxia. To confirmed this hypothesis, we mimic myocardial hypoxia or ischemia in vitro and in vivo, to observe Myocardial hypoxia and ischemia is a common pathology of many cardiovascular diseases such as coronary heart disease and heart failure, hypoxia and ischemia are common causes of cardiomyocyte injury. Pathological mechanism of myocardial hypoxia and ischemia has not been fully elucidated. RNase L was originally discovered to play a key role in the process of IFN-mediated virus resistance, its role in cardiomyocyte has not beencardiomyocyte apoptosis and related signal pathway changes in vitro using molecular biology and flow cytometry method, and to observe changes of heart function in gene knock-out mice, after up-regulation or down-regulation expression of RNase L. Reporting gene technology will also be used to study the relationship between RNase L and HIF-FIH. This study will provide a new view to clarify molecular mechanisms of myocardial hypoxia, and provide prevention and treatment targets of cardiovascular diseases such as myocardial infarction and heart failure.

心肌缺氧缺血是冠心病和心力衰竭等多种心血管疾病的共同病理过程，缺氧缺血是造成心肌细胞损伤的常见原因。目前心肌缺氧缺血的病理机制尚未完全阐明。核糖核酸酶 L（RNase L）最初被发现在IFN介导的抗病毒过程中发挥关键作用，其在心肌中的作用还未被报道。本项目前期研究首次发现心肌细胞缺氧后RNase L表达下调，我们推测缺氧时心肌细胞中的RNase L参与心肌细胞凋亡进程，这可能是心肌细胞耐受缺氧缺血的一个新机制。为了证实这一假说，我们在体内体外两个水平复制离体心肌细胞缺氧复氧和小鼠缺氧-缺血再灌注模型，采用分子生物学、流式细胞术等方法，观察上调或下调心肌细胞RNase L后，细胞凋亡和相关信号通路的变化，以及小鼠心功能变化。并利用报告基因技术探讨RNase L与HIF-FIH的相互作用。本课题将从新的视角阐明心肌缺氧缺血发生发展的分子机制，并为诸如心肌梗死，心力衰竭等疾病的防治提供靶点。