VP22-Hoxa3修饰糖尿病源性Gr-1+CD11b+髓样细胞治疗缺血性心脏病的实验研究

项目名称： VP22-Hoxa3修饰糖尿病源性Gr-1+CD11b+髓样细胞治疗缺血性心脏病的实验研究

项目编号： No.81470388

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 黄建华

作者单位： 锦州医科大学

项目金额： 73万元

中文摘要： 研究表明转录因子Hoxa3可纠正因糖尿病而受损的Gr-1+CD11b+髓样细胞和内皮细胞功能，可是，用Hoxa3同时作用于这2种细胞是一个挑战。VP22具有蛋白转导功能，且我们的预实验发现静脉注射VP22-Hoxa3修饰的糖尿病源性Gr-1+CD11b+髓样细胞可改善糖尿病小鼠的缺血心脏功能。因此我们假设：VP22-Hoxa3可同时作用于Gr-1+CD11b+髓样细胞和内皮细胞，用于并发糖尿病的缺血性心脏病的治疗。本研究用慢病毒介导VP22-Hoxa3修饰糖尿病源性Gr-1+CD11b+髓样细胞，通过细胞分选、基因转导、动物实验、蛋白印迹、qPCR、RNA干扰等方法，明确修饰后的糖尿病源性Gr-1+CD11b+髓样细胞产生的VP22-Hoxa3同时作用于自身和内皮细胞，纠正因糖尿病而受损的细胞功能，促进缺血心脏的血管新生；进一步阐明其作用机制，为并发糖尿病的缺血性心脏病的治疗提供新途径。

中文关键词： 缺血性心脏病；血管新生；糖尿病；Gr-1+CD11b+髓样细胞；细胞治疗

英文摘要： It was found that transcriptional factor Hoxa3 corrects the impaired functions of Gr-1+CD11b+ myeloid cells and endothelial cells caused by diabetes,however,it is a challenge to correct the functions of these 2 types of cells with the Hoxa3 concurrently. VP22 has the ability of protein transduction，and our prelimilary experiments showed that intravenous administration of VP22-Hoxa3 modified Gr-1+CD11b+ myeloid cells from diabetic mice improves the function of ischemic heart in diabetic mice. Thus,we hypothesized VP22-Hoxa3 could target both Gr-1+CD11b+ myeloid cells and endothelial cells concurrently for the treatment of ischemic heart disease complicated with diabetes. We plan to utilize lentiviral mediated- VP22-Hoxa3 to modify Gr-1+CD11b+ myeloid cells from diabetic mice, by cell sorting, gene transduction, animal experiment,western blot, qPCR and RNA interference et al, we will determine that VP22-Hoxa3 produced by VP22-Hoxa3 modified Gr-1+CD11b+ myeloid cells from diabetic mice targets both Gr-1+CD11b+ myeloid cells and endothelial cells concurrently, corrects the impaired cell functions caused by diabetes, and promotes the angiogenesis of ischemic heart complicated with diabetes. At mean time, we will futher elucidate the mechanism of promoting angiogenesis by VP22-Hoxa3 modified Gr-1+CD11b+ myeloid cells. This will provide a new way for the treatment of ischemic heart disease complicated with diabetes.

英文关键词： ischemic heart disease;angiogenesis;diabetes;Gr-1+CD11b+ myeloid cell;cell therapy