心肌干细胞移植可短期内改善心肌梗死心电生理稳定性和提高室颤阈值  

Short-term efficacy of cardiac stem cells in improving the electrophysiological stability and ventricular fibrillation threshold after myocardial infarction

作　　者：钟婷婷[1] 侯婧瑛[1] 郭天柱[1] 郑韶欣[1] 周长青[1] 龙会宝[1] 伍权华[1] 吴浩[1] 王彤[1] 

机构地区：[1]中山大学孙逸仙纪念医院急诊科,广东省广州市510120

出　　处：《中国组织工程研究》2015年第28期4537-4543,共7页Chinese Journal of Tissue Engineering Research

基　　金：国家自然科学基金(81270213)"ANGⅡ/AT1/SMAD/CX43通路在心肌干细胞提高心梗大鼠心电生理学稳定性和室颤阈值的作用机制研究";国家自然科学基金(81070125)"抗凋亡与促血管生成miRNA-378干预MSCs治疗心梗后心衰的机制研究";广东省科技计划项目(2010B031600032)"抗凋亡与促血管生成mi RNA-378干预MSCs治疗心梗后心衰的机制研究";广东省科技计划项目(2014A020211002)"LncRNA-Bvht/MESP1/N-cadherin通路调控MSCs向心肌细胞定向分化的机制研究";高校基本科研业务费中山大学青年教师重点培育项目(13ykzd16)"PPAR-γ/TGF-β1/Smad/CX43通路在PPAR-γ干预MSCs治疗心梗后心衰的疗效及机制研究"~~

摘　　要：背景:课题组前期研究已证实心肌干细胞移植中期(6周)能有效改善心肌梗死大鼠的心电生理稳定性和室颤阈值。目的:比较心肌干细胞和骨髓间充质干细胞移植对心肌梗死大鼠心电生理学稳定性和室颤阈值的短期疗效差异。方法:取30只健康雄性SD大鼠,开胸结扎大鼠的左前降支冠状动脉建立心肌梗死动物实验模型,随机分成3组,分别为心肌干细胞移植组,骨髓间充质干细胞移植组,PBS对照组,每组10只。分别于建模成功2周后在梗死区心肌内局部注射0.1 m L PBS悬浮的5×106 PKH26标记的心肌干细胞、0.1 m L PBS悬浮的5×106 PKH26标记的骨髓间充质干细胞及0.1 m L PBS。植入2周后,再次开胸检测大鼠心脏梗死区、梗死边缘区、非梗死区的心电生理特性和室颤阈值。实验结束后,分离心脏梗死边缘区进行病理切片及荧光显微镜检查PHK26标记的心肌干细胞和骨髓间充质干细胞缝隙连接蛋白43表达情况。结果与结论:心肌干细胞移植组单极电图纠正的激动恢复时间离散度、电刺激所激发的恶性心律失常及梗死区、梗死边缘区、非梗死区的室颤阈值与PBS组、骨髓间充质干细胞移植组相比差异有显著性意义(P<0.05);骨髓间充质干细胞移植组单极电图纠正的激动恢复时间离散度及非梗死区的室颤阈值与PBS组相比差异有显著性意义。病理结果提示在心肌干细胞组、骨髓间充质干细胞组梗死边缘区发现有心肌干细胞、骨髓间充质干细胞的存在。通过组织免疫荧光检测,PKH26标记的心肌干细胞表达较多的缝隙连接蛋白43,而PKH26标记的骨髓间充质干细胞很少表达缝隙连接蛋白43,PBS组不表达缝隙连接蛋白43。上述结果提示心肌干细胞移植短期内心电生理学特性改善的效应较骨髓间充质干细胞优越,且改善效应与缝隙连接蛋白43相关。BACKGROUND：Our previous work demonstrated that cardiac stem cel s （CSCs） transplantation could significantly improve the electrophysiological stability and ventricular fibril ation threshold in rats with myocardial infarction.OBJECTIVE：To compare the influence of CSCs and bone marrow mesenchymal stem cel s （BMSCs） transplantation on the electrophysiological stability and ventricular fibril ation threshold in rats with myocardial infarction in the short term. METHODS：Thirty male healthy Sprague-Dawley rats were selected to make myocardial infarction models induced by the left anterior descending coronary artery ligation. Then, animals were randomly divided into three groups, CSCs group, BMSCs group and the PBS group, with 10 rats in each group. Two weeks after modeling, animals were respectively given the injection of 5x106 CSCs labeled with PKH26 in 0.1 mL PBS, 5x106 BMSCs labeled with PKH26 in 0.1 mL PBS or 0.1 mL PBS alone into the infracted anterior ventricular free wal . Two weeks after intervention, the electrophysiological characteristics and ventricular fibril ation threshold were measured respectively at the infarct zone, the infarct marginal zone and the non-infarct zone. Labeled CSCs and BMSCs were detected, and the expression of connexin-43 was examined in 5 μm cryostat sections from the infarct marginal zone of each heart. RESULTS AND CONCLUSION：Compared with the BMSCs group and PBS group, significant differences were revealed in the correct unipolar electrograms activation recovery time dispersion （ARTcd）, electrical stimulation-induced malignant ventricular arrhythmias and ventricular fibril ation threshold at the infarct zone, the infarct marginal zone and the non-infarct zone in the CSCs group （P〈0.05）. Obvious differences were discovered in the ARTcd, electrical stimulation-induced malignant ventricular arrhythmias and ventricular fibril ation threshold on the non-infarct area in the BMSCs group in contrast to the PBS group. Labeled CSCs or BMSCs were identified at th

关 键 词：干细胞 移植 心肌干细胞 细胞移植 骨髓间充质干细胞 心律失常 心电生理学特性 室颤阈值 心肌梗死 国家自然科学基金 

分 类 号：R394.2[医药卫生—医学遗传学]