miR-126-3p/ITGA6信号轴调控扩张型心肌病生物学功能和左心室功能的作用及机制

扩张型心肌病（DCM）是心力衰竭和心源性猝死常见病因，但发病机制尚不明确。前期研究发现，DCM患者血浆中miR-126-3p水平明显降低，相关性分析显示miR-126-3p低表达与DCM患者左心室功能降低有关。生物信息学预测发现，miR-126-3p与整合素α6（ITGA6）的3’UTR区存在结合位点。KEGG分析ITGA6位于PI3K/AKT信号通路上游，与细胞增殖、凋亡及纤维化有关。推测DCM低表达的miR-126-3p可能靶向促进ITGA6表达，调控心肌细胞和左心室功能。本项目拟通过实验，明确DCM患者血浆中miR-126-3p表达与左心室功能的相关性；明确miR-126-3p调控ITGA6对心肌细胞生物学功能及心肌纤维化影响的机制；构建DCM大鼠模型，明确体内miR-126-3p调控ITGA6对DCM左心室功能影响的机制，为阐明DCM发病机制提供新思路，为DCM治疗提供新靶点。

Dilated cardiomyopathy (DCM) is a heart disease characterized by left ventricular dilation with systoli dysfunction. DCM is a common cause of human heart failure and sudden cardiac death, and its pathological mechanism is still unclear. Recent studies have shown that miRNAs are kind of novel non-invasive biomarker of cardiovascular disease, which can play an important role as a clinical indicator and therapeutic target in the etiology of DCM. According to our previous study, high throughput miRNAs microarray found that the plasma level of miR-126-3p was significantly decreased in patients with DCM, which was associated with the decreased left ventricular function. In addition, it was predicted by bioinformatics that miR-126-3p had binding sites in the 3’UTR region of Integrin α6 (ITGA6). KEGG analysis shows that ITGA6 is one of upstream molecules of the PI3K/AKT signaling pathway, which is related to cell proliferation and apoptosis cycle and fibrosis. Thus, it is speculated that the low expression of miR-126-3p in DCM may target ITGA6 and promote its expression to regulate the functions of cardiomyocytes and left ventricle. In vivo and in vitro experiments were carried out in this project to clarify the correlation between the expression of miR-126-3p in plasma of DCM patients and left ventricular function and explore the biological function of cardiomyocytes and myocardial fibrosis of miR-126-3p and its mechanism and investigate the effects of miR-126-3p by regulation of ITGA6 on DCM left ventricular cardiac function in vivo and its mechanism through the establishment of DCM rat models. This study will provide a new idea to elucidate the pathogenesis of DCM and a novel target and direction for the treatment of DCM.