CXCR7基因转染的内皮祖细胞促进糖尿病缺血性血管生成研究

项目名称： CXCR7基因转染的内皮祖细胞促进糖尿病缺血性血管生成研究

项目编号： No.81200239

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： 晏小清

作者单位： 温州医科大学

项目金额： 23万元

中文摘要： 糖尿病人因高血糖，其外周循环中的内皮祖细胞(EPC)数量锐减，与内皮粘附及掺入血管能力下降，血管生成能力受损，导致多种糖尿病血管并发症的发生与恶化。体内动员或体外移植EPC能够缓解病情。EPC参与血管生成受SDF-1调控，我们最新研究发现：SDF-1新受体CXCR7在人脐带血EPC中低表达，单独介导SDF-1诱导EPC存活，并促进EPC粘附、跨内皮迁移和管样结构形成。提高受体表达量能够提高细胞对生化因子的响应。鉴于CXCR7可介导多种高血糖环境中受损的EPC功能，且在EPC中低表达，我们设想提高EPC中CXCR7表达量，能够提高其在高糖环境存活和血管生成能力。本项目拟通过腺病毒转染提高EPC内CXCR7的表达，利用体外实验及糖尿病小鼠后肢缺血模型考察高表达CXCR7对EPC参与糖尿病血管生成的促进作用，论证高表达CXCR7的EPC作为糖尿病治疗性血管生成种子细胞的可行性，并探讨其分子机制。

中文关键词： CXCR7；内皮祖细胞；糖尿病；血管生成；抗氧化

英文摘要： Hyperglycosemia in diabetic patients reduces the number of endothelial progenitor cells (EPC) in peripheral circulation, impairs adhesion to endothelium and tuber formation of remaining EPC, damages angiogenesis and induces development and aggravation of multiple diabetic blood vessel complications. Mobilizing or transplanting EPC can relieve pathogenetic condition. The process EPC participating in angiogenesis is regulated by SDF-1. Our latest research showed that CXCR7, a new defined receptor of SDF-1, is low expressed in EPC. It mediates SDF-1 inducing EPC survival exclusively, and promotes EPC adhesion to endothelium, trans-endothelial migration and tube formation. Enhancing receptor expression can improve cell response to biochemical factor. Considering that CXCR7 can mediate multiple functions of EPC impaired in diabetic condition, we propose hypotheses that enhancing CXCR7 expression in EPC can improve EPC survival and its angiogenesis capability in hyperglycosemia. In this project, we will enhance CXCR7 expression in EPC by adenovirus transfection, and evaluate capability of high CXCR7 expressing EPC in promoting diabetic angiogenesis by in vitro experiments and diabetic hindlimb ischemia mice model, to assess the practicality of applying high CXCR7 expressing EPC as "seed cells" in therapeutic angiogene

英文关键词： CXCR7；endothelial progenitor cells；diabetes；angiogenesis；anti-oxidant