低氧诱导因子促缺血下肢血管新生的可行性研究  

Feasibility of hypoxia inducible factor gene transfer in endothelial progenitor cell for vascular regeneration

作　　者：姜萌[1] 王彬尧[1] 王长谦[1] 何奔[1] 范华骅[1] 邵琴[1] 黄定九[1] 

机构地区：[1]上海交通大学医学院附属仁济医院心内科,上海200001

出　　处：《心脏杂志》2008年第1期28-33,共6页Chinese Heart Journal

基　　金：国家自然科学基金项目资助(30170365)

摘　　要：目的低氧诱导因子-1α(Hypoxia inducible factor-1α,HIF-1α)是低氧环境中起细胞调控作用的关键基因。探讨HIF-1α在细胞中的过表达是否有利于缺血性疾病的治疗。方法在体外通过腺病毒介导人HIF-1α基因(Ad-HIF-1α)入人外周血内皮祖细胞(endothelial progenitor cells,EPC),观察转染后EPC的扩增及迁移功能改变及其在裸鼠缺血下肢局部的促血管新生作用。结果转染Ad-HIF-1α后的EPC在体外细胞扩增数成倍增加,迁移功能改善(P<0.05);移植异种Ad-HIF-1α-EPC至BALB/c鼠缺血下肢后可见外源性EPC定向作用于缺血部位。Ad-HIF-1α-EPC较对照组进一步促进体内毛细血管数目增加(P<0.05),缺血面积减小(P<0.05)、缺血下肢的坏死/自体离断降低60%。结论在体外,Ad-HIF-1α感染后的EPC扩增及迁移功能改善;在体内,可促进缺血下肢的局部血管新生。AIM To explore whether the overexpression of hypoxia inducible factor-1α （HIF-1α） is beneficial in cell therapy of hypoxia-induced ischemic disease. METHODS Adenovirus mediated human HIF-1 （ Ad-HIF-1 ） was transduced in human endothelial progenitor ceils （EPC） in vitro. Heterologous EPC transduced with adenovirus encoding HIF-1α were administered to Balb/c nude mice with hindlimb ischemia. RESULTS Augmented EPC proliferative activity and enhanced migration activity were seen in HIF-1 treated EPC （P 〈 0.05 ）. and exogenous EPC homing was observed. In vitro HIF-1- transduced EPC contributed to neovascularization in vivo. Limb necrosis reduced by 60% neovascularization in comparison with that in control animals and neovascularization was improved. CONCLUSION In vitro, Ad-HIF-1-EPC gene transfer enhances EPC proliferation and migration. In vivo, gene-modified EPC facilitate the strategy of cell transplantation to augment naturally impaired neovascularization in an animal model of experimentally induced limb ischemia.

关 键 词：低氧诱导因子-1Α 内皮祖细胞 缺血 血管新生 低氧 

分 类 号：R322.1[医药卫生—人体解剖和组织胚胎学]