冠心病是病死率最高的心血管疾病，血管内皮功能紊乱和胰岛素抵抗（IR）间的恶性循环是其发生发展的关键环节。围冠脉心外膜脂肪（PEAT）在调控IR诱导的冠脉粥样硬化的过程中发挥重要作用。我们前期研究发现PEAT分泌的omentin-1可抑制血管内皮细胞损伤及IR；而IR患者会出现PEAT肥大、白色/米色脂肪比例增高，致局部炎症浸润、omentin-1及adiponectin的表达降低。据此我们推测IR可能会改变PEAT的结构，抑制有益脂肪因子表达，诱导巨噬细胞趋化与极化，加重冠脉损伤；若降低PEAT中白色/米色脂肪比例，能减轻IR的不利影响，达到冠脉保护作用。本研究拟采用器官切片培养、分子生物学和细胞生物学技术，结合体外细胞模型和大动物实验，研究IR诱导PEAT重构的具体机制，及PEAT相关脂肪因子对冠脉的调控作用，以期找到脂肪改造的基因治疗方法，为冠心病合并IR的治疗提供新思路和理论基础。

Coronary heart disease is a kind of the cardiovascular disease with highest mortality in the world, the vicious cycle between vascular endothelial dysfunction and insulin resistance (IR)is the key link in its development. Pericardial epicardial adipose tissue (PEAT) plays an important role in the regulation of IR-induced coronary atherosclerosis (CA). Our previous study has found that omentin-1 secreted by PEAT can inhibit vascular endothelial cell injury and insulin resistance . In insulin resistance patients, PEAT hypertrophy, increased white / beige fat ratio, local inflammatory infiltration and decreased omentin-1 and adiponectin expression were noted. Therefore, we speculate that IR may change the structure of PEAT, inhibit the expression of beneficial adipokines, induce chemotaxis and polarization of macrophages and aggravate coronary lesions. If the ratio of white / beige fat in PEAT is decreased, the adverse effects of IR can be reduced,contributing to coronary protection. This study intends to use organ slice culture, molecular biology and cell biology techniques, combined with in vitro cell models and animal experiments to study the specific mechanisms of IR-induced PEAT remodeling, and the regulation of PEAT-related adipokines on coronary artery, in order to find The possibility of fat-remodeling gene therapy and to provide new ideas and theoretical basis for the treatment of patients with coronary heart disease complicated with IR.