SVV基因调控下的血管内皮细胞在治疗外周缺血性疾病中的应用及机制研究

项目名称： SVV基因调控下的血管内皮细胞在治疗外周缺血性疾病中的应用及机制研究

项目编号： No.81200230

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： 王学虎

作者单位： 重庆医科大学

项目金额： 23万元

中文摘要： 人口老龄化、饮食结构等因素导致外周动脉疾病（PAD）发病率逐年升高，内皮细胞在血管再生及维持血管通畅中起重要作用。我们研究发现存活素（SVV）在肿瘤细胞和血管内皮细胞中有强大的抗凋亡、促增殖及促迁移作用，但在血管内皮细胞中表达水平低。因此本研究拟通过上调SVV基因表达，获得耐凋亡、增殖活性高及易于组织浸润的内皮细胞，以期改善临床PAD的缺血状态。本研究以腺病毒为载体，采用基因转染的方式，上调血管内皮细胞SVV表达，探讨细胞的抗凋亡、增殖、浸润迁移能力的变化及机制。将获得的过表达SVV基因的内皮细胞，并进行动物体内研究，一方面研究血管内皮细胞在缺血组织中生长及浸润能力，观察缺血组织的微血管密度及肢体缺血的变化；另一方面，将内皮细胞预衬到移植生物血管内表面，探讨预衬内皮细胞的生物血管在移植后抗血栓、内膜增生及维持血管通畅的作用，为PAD的治疗提供一定的理论和实验基础。

中文关键词： 存活素；内皮细胞；外周动脉疾病；微血管密度；血管移植

英文摘要： The morbidity of peripheral vascular disease is gradually increasing in recent years. Vascular endothelial cells(VECs) play an important role in angiogenesis and the maintenance of vascular patency. Our prior study found that survivin gene has significant effect on antiapoptosis, proliferation, migration and invasion while have high expression in tumor cells and low expression in VECs. This study plan to obtain specific VECs which have high growing activity upregulate, antiapoptosic property and apt to migrate and invade through upregulating the expression of SVV gene. As the result, the VECs may are accessible to alleviate the ischemic state of the PAD. In this study, we use gene transfer techniques to upregulate SVV gene expression by the adenovirus vectors.Firstly, we will identify the mechanism of apoptosis, proliferation, migration and invasion in ECs and the change of biological function. Then, We will carry out the change after the ECs transplantion with high expression of SVV in vivo. On the one hand, we will observe the changes of microvascular density in ischemic tissue and limb; On the other hand, we will pre-lining the Ecs into inner surface of the transplantation biological blood vessel and detect the effect of the anti-thrombosis, intimal hyperplasia and maintain patency. And so for our study will

英文关键词： Survivin；Endothelial cell；Periphery artery disease；Microvessel density；Vasotransplantation