内脏脂肪细胞来源微泡中的miR-143在糖尿病心肌病中的作用与机制研究

糖尿病心肌病是糖尿病人发生心衰的主要原因之一，其发病机制尚未完全阐明。大量研究表明miRNA在糖尿病心肌病发生发展中发挥重要作用。分泌型microRNA介导的器官间通讯在疾病中的作用受到了越来越多的关注。然而其他组织器官远距分泌的miRNA在糖尿病心肌病中的作用仍不明确。在前期研究中我们通过高通量测序在糖尿病心肌病小鼠模型中筛选出miR-143，并在细胞实验中初步证明原代提取的附睾脂肪细胞可通过微泡分泌miR-143至心肌细胞。本项目将利用miR-143全身性及脂肪特异性基因敲除小鼠、脂肪移植技术和细胞模型，进一步研究内脏脂肪来源微泡中的miR-143在糖尿病心肌病中的作用及机制，从而为糖尿病心肌病的防治提供新的思路。

Diabetic cardiomyopathy is among the main risk factors of heart failure in diabetic patients, but its underlying pathophysiological mechanisms are not yet fully understood. It is well documented that microRNAs play fundamental roles in diabetic cardiomyopathy. Advancing evidence has indicated that the crosstalk between tissues via long-range endocrine of microRNA may participate in the pathological processes. However, it remains unclear whether and how extracellular microRNA delivering from other tissues to heart works in diabetic cardiomyopathy. In the preliminary study of this project, miR-143 in microvesicles was selected by microRNA sequencing in high-fat diet induced diabetic cardiomyopathy mice model. Moreover, we found microvesicles derived from isolated diabetic epididymal adipocytes could lead to the upregulation of miR-143 in HL-1 cells. In this project, we will use different type of miR-143 knockout mice and the cell models to investigate whether miR-143 was delivered from epididymal adipocytes to cardiomyocytes in vivo, and the following role of adipose-derived miR-143 in the occurrence and development of diabetic cardiomyopathy. The findings might provide new perspective for the treatment of diabetic cardiomyopathy.