诱导型多能干细胞分化的心肌细胞移植对心梗大鼠心功能改善机制的研究  

Mechanism of induced pluripotent stem cell-derived cardiomyocytes on cardiac function after myocardial infarction in rats

作　　者：姜昕 罗特丹 李鹏 

机构地区：[1]暨南大学第二临床医学院深圳市人民医院老年病科,广东深圳518020

出　　处：《中国地方病防治》2017年第8期841-843,共3页Chinese Journal of Control of Endemic Diseases

基　　金：国家自然科学基金资助项目(No.81401570);深圳市科技创新委资助项目(No.JCYJ 20130402101926972)

摘　　要：目的本研究的目的是在大鼠心梗模型中,应用诱导多能干细胞(i PSC)分化的心肌细胞(i PSC-CMs)移植,研究i PSC-CMs移植对心梗的修复及心功能改善的作用机制。方法结扎鼠冠状动脉前降支制作心肌梗死(MI)模型,分别在心梗及心梗边缘区注射总量30ul 4×10~5 iPS-CMs(iPS-CMs组)和等量的PBS(MI组)。细胞移植后4周应用心脏超声评价心脏功能改变,TUNEL法检测心肌细胞凋亡,ELISA分析细胞移植后的促血管生成蛋白的表达。结果心脏超声结果显示移植4周后,与MI组相比,iPS-CMs组左心室射血分数改善明显(LVEF,52.7±4.52%vs 41.82±6.31%,n=8,P<0.05),并且心肌细胞凋亡率显著下降(29.33±9.86%vs 44.63±10.25%,P<0.05)。ELISA结果显示i PS-CMs组可以促进血管生成素蛋白(angiopoietin-1)和血管内皮生长因子(VEGF)的表达。结论 i PS-CMs移植治疗心梗可以改善心脏功能,其机制是抑制自体心肌细胞的凋亡以及调控促血管生成蛋白的表达。Objective The purpose of this study is to investigate the mechanism of heart function improvement using human induced pluripotent stem cells（ i PSC-CMs） for myocardial repair in a rat model of myocardial infarction（ MI）.Methods Animals induced with MI model by LAD ligation were randomly assigned to receive direct intramyocardial injection of 4 × 105 i PS-CMs（ i PS-CMs group） or PBS（ MI group） at the infarct and border zone. The heart function changes,myocardial cell apoptosis and proangiogenic proteins expression was evaluated 4 weeks after i PS-CMs transplantation.Results The LVEF was significantly increased and native cardiomyocytes apoptosis was significantly reduced in i PS-CMs group compared with the MI group（ 52.7 ± 4.52% vs 41.82 ± 6.31%,and 29.33±9.86% vs 44.63± 10.25%,n = 8,P 0. 05） 4 weeks after cell transplantation. ELISA result showed i PS-CMs transplantation can upgrade the expression of angiopoietin-1 protein and vascular endothelial growth factor（ VEGF）.Conclusion Our results suggest that transplantation of i PSC-CMs can improve the heart function via restrain the native cardiomyocytes apoptosis and upgrade the expression of the proangiogenic proteins after transplantation in MI rat models.

关 键 词：诱导多能干细胞 心肌梗死 心功能 

分 类 号：R542.22[医药卫生—心血管疾病]