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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(UCG)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LAD 4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 investigate the effect of transplanted Cx43 SMC on acute myocardial infarction (AMI) in dogs and to investigate the effect of transplanted Cx43 SMC on myocardial structure and cardiac function. Methods 24 healthy mongrel dogs were randomly divided into 3 groups (n = 8): myoblast (SMC) transplantation group, Cx43 SMC transplantation group and control group. The canine autologous skeletal muscle was isolated, cultured and transformed in vitro. The plasmid vector pLenti6 / V5-DEST-Cx43 was transferred into skeletal muscle myoblasts. The animal model of AMI was established by ligating the left anterior descending artery (LAD). The experimental group was injected with SMC or Cx43 SMC (2 × 10 ~ 6 cells in total) by injecting LAD into the infarct area. Of cell culture fluid. The left ventricular ejection fraction (LVEF), left ventricular end-diastolic dimension (LVDD) and left ventricular end-systolic diameter (LVSD) were measured by echocardiography (UCG) at 1 day before AMI, ); And pathological examination of myocardial tissue light and electron microscopy. Results Left ventricular morphology and systolic function were normal in UCG before AMI. LVEF decreased, LVDD and LVSD increased after LAD for 4 weeks (P <0.05). At 4 weeks after transplantation, LVEF increased and LVDD and LVSD decreased in SMC and Cx43 SMC transplantation groups (P <0.05) compared with those in control group and pre-transplantation group. Cx43 SMC transplantation group was significantly more than SMC transplantation group (P < 0.05). Histopathological examination also showed that the engraftment of Cx43 SMC was ordered in the host myocardium in the same direction as the host cardiomyocytes with intercalated disc formation. Conclusion Myocardial transplantation of Cx43 SMC infarct area can reduce the process of ventricular remodeling, increase myocardial contractility and improve cardiac function.