间充质干细胞移植早期对心肌细胞凋亡及左心室功能的影响

Effect of early transplanted mesenchymal stem cells on apoptosis of myocardial cells and function of left ventricle

目的研究骨髓间充质干细胞(mesenchymal stem cells,MSC)缺血心肌内移植早期对心肌细胞凋亡、血流动力学及左心室功能的影响。方法采用密度梯度离心+贴壁培养方法分离培养Wistar大鼠MSC,结扎左前降支建立急性心肌梗死(AMI)模型,结扎后30min随机分为MSC组(于梗死边缘分4点心肌内注射1×106/0.1ml的MSC,10只),AMI组(同法心肌内注射PBS 0.1ml,10只),假手术组(SHAM组,5只)。监测细胞移植后72h血流动力学、超声心动图及TUNEL心肌细胞凋亡的变化。结果与SHAM组相比,AMI大鼠血流动力学恶化,表现为平均动脉压、左心室收缩压明显下降,左心室舒张末压显著升高,左心室射血分数及缩短分数均显著降低,梗死及缺血区心肌细胞凋亡比例分别为41.6%和18.9%;MSC移植减少梗死及缺血区心肌细胞凋亡32%和51%(P均<0.01),但对大鼠的平均动脉压、左心室收缩压、左心室舒张末压及左心室功能无明显改善作用(P均>0.05)。结论 MSC移植早期能减少心肌细胞凋亡但不改善急性心肌梗死后大鼠的心功能。

Objective To study the effect of early transplanted bone marrow-derived mesenchymal stem cells （MSC） on apoptosis of myocardial cells, hemodynamics and function of left ventricle （LV） in rats following acute myocardial infarction （AMI）. Methods MSC were isolated from Wistar rats by density gradient centrifugation and incubated with adherent culture method. A rat AMI model was established by permanent ligation of the left anterior descending coronary artery. Thirty minutes later, the animals were randomly divided into MSC group （n=10）, AMI group （n=10）, and sham operation group （n=5）. Apoptosis of myocardial cells, hemodynamics and function of LV were monitored by echocardiography and TUNEL 72b after transplantation of MSC. Results The mean arterial blood pressure, left ventricular systolic pressure, left ventricular ejection fraction, and shortened fraction were significantly lower while the left ventricular end diastolic pressure was significantly higher in AMI group than in sham operation group. The rate＇ of cardiac infarction and apoptosis of myocardial cells was 41.6% and 18.9%, respectively, which decreased to 32% and 51%, respectively, after MSC transplantation （P〈0.01）. However, no significant difference was found in the mean arterial blood pressure, LV systolic pressure, end LV diastolic pressure and LV function between the two groups （P〉0.05）. Conclusion Early MSC transplantation decreases the apoptosis of myocardial cells but cannot improve the left ventricular function of rats following AMI.