项目名称： 去乙酰化酶SIRT6优化老年hMSCs移植改善梗死后心脏功能的作用及机制研究

项目编号： No.81500203

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 姚杰

作者单位： 浙江大学

项目金额： 18万元

中文摘要： 干细胞移植可以显著改善梗死后心脏功能，但临床研究的效果却不明显，使此治疗方法陷入低谷。我们前期研究发现：年龄是产生这种差异的主要原因。Sirtuin蛋白具有广泛的生物学功能，最新研究发现SIRT6是抗衰老的新靶点。因此，我们推测 SIRT6可以使老年人骨髓间充质干细胞（hMSCs）年轻化，提高其旁分泌能力，从而增强其移植对缺血性心脏病治疗效果。本项目在前期研究基础上，利用心肌梗死动物模型，采用心脏超声、分子生物学、shRNA、基因转染等技术，深入研究SIRT6干预老年hMSCs在缺血性心脏病中的作用及机制；同时体外探索SIRT6增强细胞功能的作用及机制。本课题以抗衰老因子SIRT6为契入点，探讨增强老年hMSCs移植损伤修复的分子机制，为老年缺血性心脏病人的治疗提供新靶点。

中文关键词： 去乙酰化酶6；骨髓间充质干细胞；心肌梗死；老年；旁分泌

英文摘要： Stem cell transplantation can significantly improve cardiac function after myocardial infarction, but the effects of clinical study are not obvious that make this treatment in a slump. Our preliminary study suggested that the age of both the recipients and donors mainly influenced the outcome. Sirtuins protein have a wide range of biological functions, the latest research found that SIRT6 is the new target of rejuvenation. Therefore, we hypothesized that SIRT6 can make the elderly human bone marrow mesenchymal stem cells (hMSCs) younger and improve its ability of paracrine, thereby enhancing its effect on ischemic heart disease. In this study, we observed the effects and mechanism of SIRT6 in elderly hMSCs for ischemic heart disease; while exploring the mechanism of SIRT6 which enhanced cell function in vitro, by using animal models of myocardial ischemia, application of echocardiography, molecular biology, small hairpin RNA, gene transfection and other techniques. This study indicates that SIRT6 acts as a new factor in the aging, explores its molecular mechanisms of enhancing the damage repair of elderly hMSCs, will provide new target for the treatment of ischemic heart disease.

英文关键词： SIRT6;MSCs;mycardial infarction;elder;paracrine