心肌干细胞和骨髓间充质干细胞改进心肌梗死大鼠室颤阈值和心电生理稳定性的对比研究

The comparison of cardiac stem cells and mesenchymal stem cells transplantation in improving the ventricular fibrillation threshold and electrophysiological stability in rats with myocardial infarction

目的 比较心肌干细胞（cardiac stem cells,CSCs）和骨髓间充质干细胞（mesenchymal stem cells,MSCs）对心肌梗死（myocardial infarction,MI）大鼠室颤阈值和心电生理学稳定性的影响.方法 通过开胸结扎30只SD大鼠左前降支冠状动脉建立心肌梗死模型,2周后随机（随机数字法）分为CSCs组、MSCs组及PBS组,每组各10只,分别于局部梗死心肌内注射PKH26荧光标记的CSCs、MSCs或等量PBS.治疗6周后,再次开胸检测梗死边缘区的心电生理特性和室颤阈值.实验结束后,摘取心脏行病理切片,检查PKH26标记的CSCs、MSCs是否在梗死边缘区内生存并表达连接蛋白43.结果 CSCs组移植6周后其梗死边缘区单极电图激动恢复时间、纠正的激动恢复时间与MSCs组及对照组比较,差异无统计学意义（P＞0.05）;CSCs组梗死边缘区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室颤阈值与MSCs组及对照组比较,差异具有统计学意义（P＜0.05）;在上述指标方面,MSCs组和PBS组比较,均差异无统计学意义（P＞0.05）.PKH26标记的CSCs在梗死边缘区内被发现并表达连接蛋白43,而PKH26标记的存在于梗死边缘区的MSCs则很少表达连接蛋白43.结论 CSCs移植和MSCs移植治疗心肌梗死是比较安全有效的,无明显致心律失常性.CSCs移植后6周其心电生理学稳定性改善和室颤阈值提高的效应较MSCs优越,CSCs是治疗心血管疾病较为理想的种子细胞.

Objective To compare the effects of cardiac stem cells （CSCs） versus mesenchymal stem ceils （MSCs） transplantation on the electrophysiological stability and ventricular fibrillation threshold （VFT） in rats with myocardial infarction （MI）.Methods In 30 Sprague-Dawley rats,the left anterior descending coronary artery ligation was carried out to induce MI.Two weeks later,animals were randomly （random number） divided into three groups：CSCs group （n =10）,MSCs group （n =10） and phosphate buffer solution （PBS） group （control group,n =10）.Rats of each group was received the injection of CSCs labeled with PKH26 （fluorescent stain） in PBS or MSCs labeled with PKH26 in PBS or PBS alone into the local infarct zone.Six weeks after the intervention,the electrophysiological characteristics and VFT were measured at the infarct marginal zone.Labeled CSCs and MSCs were detected and the expression of connexin-43 was examined in 5 μm cryostat sections from each harvested heart,respectively.Results Compared with the MSCs group,there were no significant differences in the unipolar electrogram activation recovery time （ART） and the correct ART （ARTc） in the infarct marginal zone in the CSCs group six weeks after cells transplantation （P 〉 0.05）;there were significant differences in the ARTc dispersion,induced refratory ventricular arrhythmias and VFT in the CSCs group compared with the MSCs group and PBS group （P〈0.05）;there were no obvious differences in above findings between the MSCs group and PBS group （P 〉0.05）.Labeled CSCs with PKH26 were identified in the infarct marginal zone and expressed as connexin-43.The PKH26 labeled MSCs were identified in the infarct marginal zone and rarely expressed as connexin-43.Conclusions Both CSCs and MSCs were safe and available for the treatment of myocardial infarction,also exerted as non-arrhythmogenic agents.CSCs were superior to MSCs in modulating the electrophysiological stability and improving the VFT six weeks after the cells transplantation.CSCs were ideal seed cells in the treatment of cardiovascular disease.