过表达缺氧诱导因子1α心肌干细胞能提高心肌梗死后心功能及移植细胞的存活率  

Effects of hypoxia inducible factor 1alpha gene modified cardiac stem cell transplantation on cardiac function and survival rate of transplanted cells in rats with myocardial infarction

作　　者：李沙[1] 李树仁[1] 郝清卿[1] 

机构地区：[1]河北医科大学附属河北省人民医院心内一科,河北省石家庄市050051

出　　处：《中国组织工程研究》2017年第1期103-109,共7页Chinese Journal of Tissue Engineering Research

基　　金：河北省自然科学基金项目(C2015307019)~~

摘　　要：背景:干细胞移植后最大的障碍是细胞在缺血、缺氧等恶劣环境下极低的存活率。为解决这一难题,人们尝试基因修饰的方法,即在细胞移植前将抗凋亡基因通过转染或转导的方式,使其基因结构发生改变,进而可能会从根源上解决干细胞的存活、代谢及增生或分化等能力。目的:经缺氧诱导因子1α基因修饰的心肌干细胞移植入大鼠心肌梗死边缘区后,观察移植后心肌干细胞的存活率及大鼠心功能的变化。方法:将24只SD大鼠随机等分为3组:缺氧诱导因子1α转染心肌干细胞组、心肌干细胞组和模型组,以开胸结扎冠脉的方法制备心肌梗死模型,2周后分别注射经Ad-HIF1α-eGFP转染的心肌干细胞、Ad-eGFP转染的心肌干细胞及PBS液。结果与结论:心肌干细胞移植可提高心功能;经缺氧诱导因子1α基因修饰的心肌干细胞移植可较单纯心肌干细胞移植更显著改善心功能;梗死后左室射血分数的改善与梗死边缘区心肌干细胞密度呈正相关。说明过表达缺氧诱导因子1α的心肌干细胞能有效改善心肌梗死大鼠心功能及移植细胞的存活。BACKGROUND： The biggest obstacle after stem cell transplantation is the extremely low survival rate of transplanted cells in the severe environments such as ischemia and hypoxia. In order to solve this problem, gene modification is expected to fundamentally improve the survival, metabolism and proliferation/differentiation of stem cells, namely by anti-apoptotic gene transfection or transduction prior to transplantation to vary the gene structure. OBJECTIVE： To observe the survival rate of transplanted cells and cardiac function in rats undergoing hypoxia inducible factor-lo （HIF-la） gene modified cardiac stem cell transplantation into the edgdarea of myocardial infarction. METHODS： Twenty-four Sprague-Dawley rats were used to make myocardial infarction models by ligation of coronary arteries and then randomized into HIF-la-transfected cell transplantation group, cell transplantation group and model group （n=8 per group）. Two weeks after modeling, model rats were given the injection of Ad-HIFlo-eGFP-transfected cardiac stem cells, Ad-eGFP-transfected cardiac stem cells or PBS, respectively. RESULTS AND CONCLUSION： Cardiac stem cell transplantation improved the rat cardiac function, and HIF-la transfected cardiac stem cell transplantation.showed better effects on cardiac function improvement than simple cell transplantation. Additionally, the improvement in left ventricular ejection fraction was associated with the density of cardiac stem cells in the marginal zone. To conclude, HIF-la transfected cardiac stem cell transplantation can effectively improve the cardiac function in rats with myocardial infarction.

关 键 词：干细胞 移植 缺氧诱导因子1α基因 细胞培养 流式细胞术 心肌干细胞 基因治疗 心肌梗死 免疫组织化学 河北省自然科学基金 

分 类 号：R394.2[医药卫生—医学遗传学]