胰岛素抵抗（IR）是2型糖尿病（T2DM）大血管并发症发生与发展的基础。miRNAs和DNA甲基化修饰参与T2DM大血管并发症的全程调控。有氧运动是改善IR的有效措施，机制尚未阐明。前期研究发现miR-382-3p负向调控resistin表达是有氧运动改善血管内皮IR的重要途径，在此基础上进行生物信息学预测，发现miR-382-3p启动子区域存在甲基化修饰。因此，本研究提出假说：有氧运动可能通过调节甲基化动态平衡影响主动脉内皮miR-382-3p表达，进而负向调控resistin表达，改善血管内皮IR，抑制大血管病变的发生发展。本研究拟对IR小鼠进行有氧运动干预，同时建立IR细胞模型，通过对甲基化酶DNMT1、去甲基化酶TET2进行功能缺失和过表达研究，以期阐明有氧运动对miR-382-3p甲基化修饰的调控机制，为T2DM大血管病变的防治提供实验证据和新的治疗靶点。

Insulin resistance (IR) is the basis for the occurrence and development of macrovascular complications in type 2 diabetes mellitus (T2DM).MiRNAs and DNA methylation are involved in the whole-course regulation of T2DM macrovascular complications.Aerobic exercise is an effective measure to improve IR.Previous studies have found that miR-382-3p negative control resistin expression is an important way of promoting the aerobic exercise improve endothelial IR, on the basis of the bioinformatics prediction, found that miR-382-3p promoter region methylation modification.Therefore, this study put forward the hypothesis that aerobic exercise may be affected by adjusting the methylation of dynamic balance of aortic endothelial miR-382-3p expression, and negative control resistin expression, improve endothelial IR, inhibit the occurrence of major vascular lesions.In this study, IR mice were subject to aerobic exercise intervention, IR cell model was established, and the function loss and overexpression of methylated enzyme DNMT1 and demethylase TET2 were studied, so as to clarify the regulatory mechanism of aerobic exercise on the methylation modification of miR-382-3p, and provide experimental evidence and new therapeutic targets for the prevention and treatment of T2DM large vessel disease.