心肌干细胞移植心肌梗死区12周后的心电生理稳定性及室颤阈值改善效应

摘要

BACKGROUND:Our previous work has demonstrated that the electrophysiological stability and ventricular fibrilation threshold were distinctly improved in rats with myocardial infarction 6 weeks after cardiac stem cels transplantation (short- to mid-term). OBJECTIVE: To observe the long-term effects of cardiac stem cels transplantation on the ventricular fibrilation threshold and electrophysiological stability in rats with heart failure post myocardial infarction. n METHODS: Twenty Sprague-Dawley rats with myocardial infarction were induced by the left anterior descending coronary artery ligation. Two weeks later, animals were randomized to receive the injection of cardiac stem cels labeled with PKH26 in PBS or PBS alone into the local infarct zone. Twelve weeks after the cardiac stem cels or PBS injection, the electrophysiological characteristics and ventricular fibrilation threshold were measured at the infarct zone, the infarct marginal zone and the non-infarct zone. Labeled cardiac stem cels were detected and the expression of connexin-43 and α-sarcomeric actin was examined in cryostat sections from each harvested heart. RESULTS AND CONCLUSION:Compared with the PBS group, no significant differences were revealed in the unipolar electrogram activation recovery time and the correct activation recovery time in the infarct zone, the infarct marginal zone and the non-infarct zone in the cardiac stem cels group at 12 weeks post the cel transplantation (P > 0.05). There were no remarkable differences in the correct activation recovery time dispersion and induced malignant ventricular arrhythmias between the two groups (P > 0.05). No obvious differences were discovered in the ventricular fibrilation threshold in the infarct zone and infarct marginal zone in the cardiac stem cels group in contrast to the PBS group (P > 0.05), though a statistical significance could be found in the non-infarct zone between the two groups (P < 0.05). Labeled cardiac stem cels were identified in the infarct marginal zone and expressed connexin-43 and α-sarcomeric actin. It suggested that the beneficial effects of cardiac stem cels in modulating the electrophysiological stability and improving the ventricular fibrilation threshold faded away 12 weeks after cel transplantation. However, the mechanisms involved remained unclear.%背景：课题组前期研究证实心肌干细胞治疗心肌梗死后短中期(6周)能明显改善心电生理学稳定性和室颤阈值。目的：观察心肌干细胞对心力衰竭大鼠室颤阈值和心电生理稳定性的长期影响。方法：开胸结扎20只SD大鼠左前降支冠状动脉，2周后其中10只大鼠局部梗死心肌内注射PKH26荧光标记的由PBS悬浮的心肌干细胞，另10只大鼠局部梗死心肌内注射等量PBS。治疗12周后，再次开胸检测梗死区、梗死边缘区和非梗死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PHK26标记的心肌干细胞是否在梗死区内生存并表达连接蛋白43及α-肌动蛋白。结果与结论：与对照组相比，心肌干细胞移植12周后其梗死区、梗死边缘区和非梗死区的单极电图激动恢复时间、纠正的激动恢复时间差异无显著性意义(P >0.05)；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差异无显著性意义(P>0.05)；室颤阈值方面，实验组梗死区和梗死边缘区与对照组相比差异无显著性意义(P >0.05)，非梗死区与对照组相比差异有显著性意义(P <0.05)。PHK26标记的心肌干细胞在梗死边缘区内被发现并表达连接蛋白43和α-肌动蛋白。以上结果提示心肌干细胞移植后12周其心电生理的稳定性和室颤阈值的改善效应已逐渐消失，但机制未明。