靶向SIRT1的miRNAs在糖尿病视网膜病变中的作用研究

Diabetic retinopathy (DR) is primarily a microvascular complication caused by chronic hyperglycemia of diabetes, but the molecular pathogenesis is still utterly unknown. Studies have shown that microRNAs (miRNAs) and SIRT1 are be involved in diabetes and its complications. However, the miRNAs involved in SIRT1 related biologieal proeesses during the pathogenesis of DR have not identified. This study aims to explore SIRT1 specific miRNAs expressed in RMECs of STZ-induced diabetes mellitus (DM) rat (the miRNAs targeting to SIRT1 and the SIRT1 regulated miRNAs), and elucidate their biological functions and pathways in vitro (proliferation, migration, and tubularisation) and in vivo (DM rats infected with lentivirus with SIRT1 specific miR or antigomiR), subsequently, reveal the mechanism of miRNA-SIRT1-miRNA and their role in angiogesis and DR. Our research could provide a new insight into the function of SIRT1 specific miRNAs in the development of DR and might represent a potential therapeutic strategy.

糖尿病视网膜病变（DR）是由长期高血糖引起的糖尿病微血管并发症，但分子致病机制不明。研究显示miRNAs和SIRT1与糖尿病及其并发症之间存在密切的联系，本研究以寻找DR相关因子SIRT1特异的miRNAs为切入点，激光捕获显微切割法分离DM大鼠RMECs，筛选靶向调控SIRT1和受SIRT1调控的miRNAs，利用miRNA mimics、inhibitors、target protectors和双荧光素酶报告系统验证其生物学功能、靶标和调控通路，并在体内研究SIRT1-miRNA在DM大鼠中的防治效果，探索特异性miRNA在糖尿病大鼠视网膜病变中的作用与机制，从而从一个新的层面阐明miRNA-SIRT1-miRNA在促血管生成及DR形成过程中的分子机制，为发展基于SIRT1特异miRNA的DR分子诊断、防治新策略打下基础，同时为视网膜新生血管相关性眼底疾病的防治提供新方法和理论依据。