基于microRNA探讨芪归药对干预糖尿病心肌病的机制研究

Diabetic cardiomyopathy (DCM) is an important cause of death and disability in patients with diabetes mellitus, and the prevention and treatment of diabetic cardiomyopathy is the focus of research. Invigorating Qi and promoting blood is the main treatment method of DCM in clinical. Our preliminary study confirmed that the combination of Astragalus-Angelica can reduce blood glucose,at the same time, it can effectively reduce the diabetic vascular endothelial injury mediated by inflammatory pathways to improve diabetic angiopathy. To further clarify the targets of intervention of DCM, this study aimed to study the effect of Astragalus ad Angelica Decoction on db/db mice with type 2 diabetes mellitus. By analysing the changes of miRNA expression in the myocardium of mice after the intervention of traditional Chinese medicine, clear the function of miRNA in the pathogenesis of DCM, and push the miRNA and its target mRNA in treatment of DCM. By the observation of the expression changes of mRNA and protein when blocking or activating the core miRNA in the myocardial cell H9c2, we can not only discuss the pharmacological mechanism of Astragalus ad Angelica Decoction,but also clarify the mechanism of Astragalus ad Angelica Decoction regulating miRNA in the treatment of DCM from the molecular level, and provide a theoretical basis for the study on etiology of DCM, in order to further explore the gene diagnosis and gene therapy.

糖尿病心肌病（DCM）是糖尿病患者致死、致残的重要病因，挖掘针对其病理机制的防治措施是研究的热点。临床以益气活血为主要治法，前期研究证实了益气活血药对黄芪-当归（芪归）在降低血糖的同时，能够有效减轻炎症通路介导的糖尿病血管内皮损伤，从而改善糖尿病血管病变。为进一步明确芪归药对干预DCM的作用靶点，本研究拟以芪归药对干预2型糖尿病db/db小鼠，通过差异miRNA组学分析中药干预后小鼠心肌组织miRNA表达谱的改变，明确miRNA在DCM发病机制中的作用，并推测芪归药对治疗DCM的核心miRNA及其靶mRNA；点对点观察在芪归药对干预体外培养的心肌细胞H9c2过程中阻断或激活核心miRNA时mRNA和蛋白表达的变化，从分子水平阐明芪归药对调控miRNA治疗DCM的作用机制，为DCM的病因学研究提供理论依据，以期在基因诊断和基因治疗方面进行进一步探索。

糖尿病心血管并发症是糖尿病患者致死、致残的主要原因，其中糖尿病心肌病（Diabetic cardiomyopathy,DCM）是独立于高血压、冠心病及心脏瓣膜病变的一种糖尿病心脏并发症，因其发病率和危害性极高而引起广泛关注，目前针对其病理机制现有的防治措施尚不理想。深入探讨DCM的发病机制、寻找新的相关致病基因，将对预防和诊疗DCM具有重要价值。新近研究表明，微小RNA(microRNA,miRNA）表达异常在DCM发病机制中起到重要作用。因此，本研究试图寻找DCM新的相关致病基因，通过观察黄芪-当归（芪归）药对对miRNA及其靶基因的影响，从干预炎性反应的角度阐明中药调控miRNA治疗DCM的作用原理，为DCM的病因学研究提供理论依据，以期在基因诊断和基因治疗方面进行进一步探索。