LncRNAs在糖代谢紊乱致心肌疾病中的分子机制与防治新靶点

糖代谢紊乱是心肌细胞损伤和功能障碍的重要原因，但其确切分子机制仍不清楚，临床上仍缺乏新的干预靶点和生物标志物。长链非编码RNA（lncRNAs）是一类重大心脏疾病的关键调控分子，其在糖尿病心肌病中的作用仍有待阐明。我们前期发现：1）糖尿病小鼠心肌组织中有28个差异表达lncRNA和153个差异表达mRNA；2）生物信息学分析表明其中149个mRNA为Gene Ontology节点交集基因，且这28个lncRNAs对细胞凋亡、坏死、氧化应激、钙循环的信号通路具有潜在调节作用。因此，我们假设：lncRNAs通过调控心肌细胞损伤关键蛋白与信号通路，参与糖尿病心肌病的发生发展。本项目将综合运用功能学、分子生物学等技术系统阐明一组lncRNAs调节糖尿病心肌病的作用与机制，发现新的防治靶点；同时，阐明血浆lncRNAs在糖尿病心肌病诊断和预后中的价值，发现新的生物标志物。

Diabetic cardiomyopathy (DCM) is a chronic diabetic complication characterized by myocardial changes, which can cause heart failure and its harm is serious. Glucose metabolism disorder is an important cause of cardiomyocytes injury and dysfunction, but its exact molecular mechanism is still unclear. There is still a lack of new intervention targets and biomarkers clinically for glucose metabolism disorder. Long noncoding RNAs (lncRNAs) are the key regulators of cardiac diseases, and their role in diabetic cardiomyopathy remains to be elucidated. Our previous study found that: 1) there were 28 lncRNAs and 153 mRNA differentially expressed in the myocardium of diabetic mice. 2) bioinformatics analysis showed that 149 mRNA were node overlapping genes of Gene Ontology, and these 28 lncRNAs had a potential regulatory role in the signaling pathway of apoptosis, necrosis, oxidative stress and calcium cycling. Therefore, we hypothesized that lncRNAs may play an important role in the development of diabetic cardiomyopathy by regulating the key proteins of myocardial injury and signaling pathways. In this project, we will use the comprehensive techniques of functional and molecular biology to elucidate the role and mechanism of a host of lncRNAs in the regulation of diabetic cardiomyopathy, and find new targets for prevention and treatment. Meanwhile, we will clarify the value of plasma lncRNAs in the diagnosis and prognosis of diabetic cardiomyopathy and find new biomarkers.