miRNAs/mTOR调控网络在糖尿病雷帕霉素抵抗中的作用及机制研究

尽管雷帕霉素药物洗脱支架已广泛应用，但糖尿病患者PCI术后再狭窄依然偏高。我们推测糖尿病患者可能存在雷帕霉素抵抗现象，且该现象可能与糖尿病患者miRNAs表达异常导致的雷帕霉素受体mTOR功能改变有关，并通过生物信息学及高通量基因芯片技术，筛选出4种可疑miRNAs（miR-155，miR-1207-5p，miR-545和miR-762）。本项目拟在前期研究基础上，系统研究4种miRNAs与其所调控的靶基因之间的关系，阐明miRNAs/mTOR调控网络在糖尿病雷帕霉素抵抗中的作用及其机制，为突破再狭窄防治的瓶颈提供新思路。

Despite the extensive use of rapamycin-eluting stent, patients with diabetes still show a relatively high incidence of post-PCI restenosis. We speculated that there is a rapamycin-resistance in diabetic patients, and this condition may probably associated with the changes in function of the rapamycin receptor mTOR, which is caused by the abnormal miRNA expressions of in diabetic patients, and have screened out 4 suspicious miRNAs (miR-155, miR-1207-5p, miR-545 and miR-762) through bioinformatical and high-throughput approaches. This project, based on our previous studies, is designed to systematically investigate the relations of the 4 miRNAs with their target genes, and thereby elucidate the role and mechanism of the miRNAs/mTOR regulatory network in diabetic rapamycin-resistance, so as to provide a promising strategy for prevention and treatment of post-PCI restenosis.