Cx43转基因自体成肌细胞移植对犬急性心肌梗死后心肌结构和心功能的影响  

The influence of Connexin43 transgenic autologous skeletal myoblast cells on myocardial structure and cardiac function after being transplanted into acute infarcted myocardlum in adult canine

作　　者：范慧敏[1] 汪进益[1] 刘中民[1] 洪暄[1] 孔祥[1] 赵曙光[1] 丁一[1] 

机构地区：[1]同济大学附属东方医院心胸外科,上海200120

出　　处：《中华实验外科杂志》2006年第11期1328-1330,共3页Chinese Journal of Experimental Surgery

基　　金：上海市科技发展基金(02ZB14078)

摘　　要：目的移植Cx43转基因自体成肌细胞（Cx43 SMC）到犬急性心肌梗死（AMI）区内，观察移植Cx43 SMC对心肌结构和心功能的影响。方法将24条健康杂种犬采用计算器随机法分为3组（n=8），即成肌细胞（SMC）移植组、Cx43 SMC移植组和对照组。取犬自体骨骼肌，经体外分离、培养和转化，将质粒载体pLenti6／V5-DEST-Cx43转入骨骼肌成肌细胞。利用结扎左前降支（LAD）的方法建立AMI动物模型，经LAD和梗死区多点注射的方法将实验组犬注射SMC或Cx43 SMC（细胞总数2×10^6个），对照组注射等量的细胞培养液。分别在AMI前1d、AMI后4周、细胞移植4周后，用超声心动图（UC／3）测量左室射血分数（LVEF）、左室舒张末期内径（LVDD）和左室收缩末期内径（LVSD）；并进行心肌组织的光镜和电镜的病理学检查。结果AMI前UCG检查犬左室形态和收缩功能正常，结扎LAD4周后，LVEF降低、LVDD和LVSD均增加（P〈0．05）。移植后4周，与对照组和移植前比较，SMC和Cx43 SMC移植组的LVEF升高、LVDD和LVSD减少（P〈0.05），其中Cx43 SMC移植组较SMC移植组为显著（P〈0．05）。组织病理学检查亦显示移入的Cx43 SMC在宿主心肌组织中排列有序，与宿主心肌细胞的排列方向一致，其间有闰盘形成。结论Cx43 SMC梗死区心肌移植后可减轻心室重构的进程，增加心肌的收缩力，改善心功能。Objective To study the influence of Connexin43 transgenic autologous skeletal myoblast cells （Cx43 SMCs） on myocardial structure and cardiac function after being transplanted into acute infarcted myocardial site in adult canine. Methods Autologous SMCs were aspirated from the musculus rectus femoris of thigh of adult canine. After being isolated,cultured and the plasmid pLenti6/V5-DEST- Cx43 was transfected into these skeletal myoblasts, either autologous SMCs （total cells 2 × 10^6, SMCs experimental group, n = 8） ,Cx43 SMCs （total cells 2× 10^6 ,Cx43 SMCs experimental group, n = 8）, or equal volume of culture medium （control group, n = 8）, was injected into the left anterior descending （LAD） branch of coronary artery just distal to the ligation site of the LAD. The same volume of BMSCs or culture medium was injected into several spots in the infarcted myocardium. Echocardiographic measurements were performed one day before and 4 weeks after infarction,as well as 4 weeks after implantation. Myocardial tissue was observed histopathologically to assess the myocardial structure and cardiac function. Results Compared with control group and before implantation, the left ventricular ejection fraction （LVEF） of SMCs group and Cx43 SMCs group was increased at 4 weeks after SMCs or Cx43 SMCs implantation （P 〈 0.05）,and the left ventricular end-diastolic diameter （LVDD） and left ventrlcular end-systolic diameter （LVSD） were decreased （P 〈 0.05）, suggesting cardiac function was improved. The improvement in left ventricular functions,including LVEF, LVDD and LVSD,was greater in the Cx43 SMCs group than that in SMCs group （P〈 0.05）. The transplanted Cx43 SMCs arranged orderly and Cx43 gap junctional coupling formed. Conclusion Implantation of Cx43 SMCs into the infarcted myocardium is believed to attenuate the remodeling process,and improve the contractile ability of the myocardium and cardiac function.

关 键 词：骨骼肌细胞 连接蛋白43 基因表达 心肌梗死 细胞移植 心功能 

分 类 号：R542.22[医药卫生—心血管疾病]