环状RNA（circ_0076631）靶向miR-214/133调控糖尿病心肌病的新机制

Diabetic cardiomyopathy (DCM) is one of diabetic complications, which is associated with myocardial injury and fibrosis, however, the exact pathogenesis is poorly understood. Recently, whether circRNA plays the critical role in DCM has been extensively discussed. Our preliminary results showed that cardiomyocytes treated with high glucose were accompanied with increased circ_0076631 level, decreased miR-214, increased caspase-1 and caspase-3, and aggravated apoptosis and pyroptosis; fibroblasts treated with high glucose were accompanied with increased circ_0076631 level, decreased miR-133, increased TGF-β1, and aggravated fibrosis. Therefore, we hypothesized that circ_0076631 regulated myocardial injury and fibrosis through targeting miR-214 and miR-133, respectively. In this project, we try to identify the role and molecular regulatory mechanism of circ_0076631 on DCM by biological information, transgenic technology and molecular biological technique both in vivo and in vitro.

糖尿病心肌病（DCM）是导致糖尿病患者死亡的重要并发症之一，其发生与心肌损伤和纤维化有关，但确切的发病机制尚未阐明。近来环状RNA在DCM中的重要调控作用已成为科学家关注的热点。我们前期研究发现：1）在高糖处理的心肌细胞中，circ_0076631表达增加，miR-214表达减少且其靶基因caspase-1和caspase-3表达增加，细胞焦亡、凋亡加重；2）在高糖处理的成纤维细胞中，circ_0076631表达也增加，miR-133表达减少且其靶基因TGF-β1水平增加，纤维化加重。因此我们假设：circ_0076631通过靶向miR-214和miR-133，从而分别调节心肌损伤与纤维化，进而影响DCM的发生发展。为验证这一假说，我们将联合运用生物信息、转基因和基因敲除、分子生物学等技术从离体和在体水平阐明circ_0076631在DCM中的作用与分子调控机制，并为其治疗提供新的靶点。