血管内皮生长因子联合突变型低氧诱导因子1α的促血管生成作用  

Vascular endothelial growth factor combined with mutant hypoxia-inducible factor 1alpha promotes angiogenesis

作　　者：胡亮[1] 王军海[1] 王志烈[1] 谢金元[1] 陈登[1] 丁凡[2] Hu Liang;Wang Junhai;Wang Zhilie;Xie Jinyuan;Chen Deng;Ding Fan(Department of Joint Surgery,Jingmen No.1 People’s Hospital,Jingmen 448000,Hubei Province,China;Department of Traumatic Hand and Foot Surgery,Jingmen No.1 People’s Hospital,Jingmen 448000,Hubei Province,China)

机构地区：[1]荆门市第一人民医院关节外科,湖北省荆门市448000 [2]荆门市第一人民医院创伤手足外科,湖北省荆门市448000

出　　处：《中国组织工程研究》2019年第3期378-383,共6页Chinese Journal of Tissue Engineering Research

基　　金：国家自然科学基金项目资助(81401827)项目负责人:丁凡~~

摘　　要：背景:研究表明,血管内皮生长因子的转录翻译过程在许多缺血、缺氧的条件下都会增加,有效改善机体血管形成与侧支微循环。突变低氧诱导因子1α的表达也需要严格的缺氧条件,很大程度上限制了其实际应用。目的:观察腺病毒介导的血管内皮生长因子联合突变型低氧诱导因子1α(Ad-VEGF-IRES-HIF-1αm u)转染内皮祖细胞在激素性股骨头缺血性坏死修复中促血管生成的作用。方法:①转染Ad-VEGF-IRES-HIF-1αm u到内皮祖细胞,观察细胞活性、形态及细胞病变效应;②将转染Ad-VEGF-IRES-HIF-1αm u成功的内皮祖细胞植入激素性股骨头缺血性坏死动物模型的股骨坏死部位(实验组:转染Ad-VEGF-IRES-HIF-1αm u,对照组:内皮祖细胞细胞悬液,空白组:细胞培养液);③移植10周后,检测血管内皮生长因子、低氧诱导因子1α蛋白表达及CD34表达和微血管密度计数;④墨汁灌注透明切片血管形态学观察。结果与结论:①实验组血管内皮生长因子和低氧诱导因子1α蛋白表达高于对照组与空白组(P<0.05);②实验组的CD34表达阳性的微血管数量较多,且相互之间有连接。③实验组动物股骨头血管墨汁染色显示有新的血管生成,部分血管管径良好,有再通现象,血管间有清晰的连通脉络,有效的血管脉络均匀分布在缺损区域;实验组新生血管面积显著高于对照组和空白组(P <0.05);④结果提示,血管内皮生长因子联合突变型低氧诱导因子1α在激素性股骨头缺血性坏死修复中可以增强血管生成作用。BACKGROUND:Transcription and translation of vascular endothelial growth factor has been shown to be increased under ischemic and hypoxic conditions,which effectively improves angiogenesis and collateral microcirculation in vivo.Expression of mutant hypoxia-inducible factor-1α(HIF-1αmu)requires hypoxic condition,so its application is limited.OBJECTIVE:To study the effect of transfection of adenovirus-mediated-vascular endothelial growth factor combined with HIF-1αmu(Ad-VEGF-IRES-HIF-1αmu)into endothelial progenitor cells on the angiogenesis in the treatment of steroid-induced avascular necrosis of the femoral head.METHODS:Ad-VEGF-IRES-HIF-1αmu was transfected into endothelial progenitor cells,and the cell viability,morphology and cytopathic effect were observed.Endothelial progenitor cells transfected with Ad-VEGF-IRES-HIF-1αmu were implanted into the necrotic site of the animal model of steroid-induced avascular necrosis of the femoral head(experimental group:transfected with Ad-VEGF-IRES-HIF-1αmu;control group:suspension of endothelial progenitor cells;blank group:cell culture medium).After 10 weeks of transfection,expression of vascular endothelial growth factor,hypoxia-inducible factor1αand CD34 as well as microvessel density were detected.The vascular morphology was observed by ink perfusion.RESULTS AND CONCLUSION:The expression levels of vascular endothelial growth factor and hypoxia-inducible factor1αin the experimental group were higher than those in the control and blank groups(P<0.05).The number of microvessels positive for CD34 was the argest in the experimental group.In the experimental group,the ink perfusion of femoral head showed new angiogenesis,the phenomenon of recanalization occurred in some vessels,blood vessels had a clear connectivity,and effective vascular veins evenly distributed into the defect area.The area of neovascularization in the experimental group was significantly larger than that in the control and blank groups(P<0.05).Vascular endothelial growth factor combined with mut

关 键 词：血管内皮生长因子 突变型低氧诱导因子1α 激素性股骨头缺血性坏死 血管生成 血管内皮生长因子类 缺氧诱导因子1 股骨头坏死 组织工程 

分 类 号：R446[医药卫生—诊断学]