miRNA 氧化修饰调控心脏成纤维细胞增殖及心肌纤维化分子机制研究

心肌纤维化发生在病理性心肌重构过程中，是各种心脏疾病发展为心力衰竭的重要原因。心肌纤维化涉及复杂的分子机制，心脏成纤维细胞过度增殖是重要原因之一，揭示心肌成纤维细胞增殖调控机制是研究心肌纤维化的重要方向。miRNA在心脏中发挥重要作用，与许多心血管疾病密切相关。我们首次发现了过多的活性氧（ROS）使miRNA氧化修饰，氧化修饰的miRNA参与调控心肌细胞凋亡。前期研究显示心肌成纤维细胞中也存在miRNA的氧化修饰，并初步发现氧化修饰的miR-FC参与调控心脏成纤维细胞增殖。在此基础上将进一步观察心脏成纤维增殖过程中miRNA的氧化修饰水平；深入探讨氧化修饰的miR-FC调控心脏成纤维细胞增殖的分子机制；整体动物水平探讨氧化修饰的miR-FC在心脏纤维化中的作用。研究结果将加深我们对miRNA氧化修饰特性的了解，对于揭示心脏疾病的发病机制、提出新的防治策略具有重要意义。

Myocardial fibrosis occurring in the process of pathological cardiac remodeling play a pivotal role in the development of coronary heart disease-related heart failure。A complex molecular mechanism is involved in the myocardial fibrosis; among them the excessive proliferation of myocardial fibroblasts is one of the most important reasons, suggesting that the regulatory mechanism of myocardial fibroblasts underling myocardial fibrosis is the important investigation direction. MicroRNAs (miRNAs) make an important effect on the heart, and are closely related to many cardiovascular diseases. For the first time, we found that the excessive reactive oxygen species (ROS) could make miRNAs to be oxidative modificated, and the oxidation modificated miRNA was involved in regulation of myocardial cell apoptosis. In our previous study, we found that miRNAs could also be oxidative modified in myocardial fibroblasts, and the oxidative modificated miR-FC participated in regulating cardiac fibroblasts proliferation. On the basis of the study, we will further observe the oxidative modification level of miRNAs in the process of cardiac fibroblasts proliferation, and investigate the mechanisms of proliferation on myocardial fibroblasts induced by the oxidative modificated miR-FC. In addition, we will explore the oxidative modificated miR-FC effects on cardiac fibrosis in the overall level of animals. The data of this project will deepen our understanding of the oxidative modification of miRNAs, as well as provide insights to the development of new anticancer drugs in the prevention and treatment of heart disease.