Bcl-2基因转染对高糖低氧诱导的移植内皮祖细胞损伤的保护作用及机制研究

项目名称： Bcl-2基因转染对高糖低氧诱导的移植内皮祖细胞损伤的保护作用及机制研究

项目编号： No.81200233

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 医学一处

项目作者： 吴子衡

作者单位： 浙江大学

项目金额： 23万元

中文摘要： 下肢缺血性疾病已成为危害中老年人的常见病和多发病，已失去手术和介入治疗机会的终末期患者面临截肢的严重后果。自2002年首例内皮祖细胞（EPC）移植治疗终末期下肢缺血性疾病获得成功以来，该治疗在世界范围内得到迅速开展，我们在实验和临床中也均验证了该治疗的有效性。但同时国内外大量文献表明该治疗的疗效有待提高，尤其对糖尿病性严重肢体缺血性疾病的疗效不佳，最新研究证明移植的EPC在高糖低氧环境下数量减少、功能减弱，是影响疗效的关键所在。因此,如何保护高糖低氧导致的移植EPC损伤是当前的研究热点。本课题预期通过凋亡调控基因Bcl-2转染大鼠骨髓源EPC的方法，进行转基因EPC在体外高糖低氧环境下和糖尿病大鼠缺血肢体内的抗凋亡和促新生血管生成能力的研究，从机制上证明Bcl-2基因转染对高糖低氧诱导的移植EPC损伤有保护作用，为临床上改善EPC移植治疗糖尿病性严重肢体缺血性疾病的疗效提供新思路。

中文关键词： 内皮祖细胞；Bcl-2；高糖；低氧；凋亡

英文摘要： Lower limb ischemia is common and frequently-occurring disease in the elderly nowadays, the patients with end-stage lower limb ischemia who have lost a good opportunity for surgical and interventional treatment have to face the outcome of amputation. Since the first case of endotheliar progenitor cell (EPC) transplantation for end-stage lower limb ischemia was achieved successfully in 2002, this treatment has been rapidly carried out in the world, we also confirmed the efficacy of the treatment in clinic and experiment. However, some domestic and international literature indicates that the efficacy of EPC transplantation in treating critical limb ischemia remains to be improved, especially for diabetic critical limb ischemia, recent studies have shown that high glucose hypoxia environment will reduce the number and function of transplanted EPC, maybe this is the key to the point. Therefore, how to protect transplanted EPC from high glucose hypoxia induced injury is current research focus. This proposal is expected to transfect apoptosis regulatory gene Bcl-2 in rat bone marrow-derived EPC, then measuring the anti-apoptotic ability and cell functions of genitically modified EPC in vitro high glucose hypoxia environment and in ischemic limb of diabetic rats, proving Bcl-2 gene modification has a protective effect

英文关键词： endothelial progenitor cell；Bcl-2；high glucose；hypoxia；apoptosis