骨髓间充质干细胞移植治疗大鼠心肌梗死及随后的心肺复苏(英文)

Cardiopulmonary resuscitation in myocardial infarction rats treated with bone marrow mesenchymal stem cell transplantation

背景:至目前为止发表的心肺复苏论文所使用的基本为健康动物,而临床实际情况是在心肺复苏发生之前患者大多有严重的心脏疾病,并导致了心室颤动的发生。目的:实验力图接近临床实际,观察骨髓间充质干细胞移植后心肌梗死大鼠心功能的变化,及对其心肺复苏结果的影响。设计、时间及地点:随机对照动物实验,于2007-04/08在美国南加州大学和中山大学附属第二医院联合完成。材料:成年SD雄性大鼠18只,随机分为模型对照组、细胞移植组,9只/组。另取1月龄SD大鼠1只用于制备骨髓间充质干细胞。方法:两组大鼠均结扎左前降支冠状动脉建立心肌缺血模型,4周后再次开胸,细胞移植组梗死心肌局部注射PKH26荧光标记的骨髓间充质干细胞悬液0.1mL(5×106个细胞),模型对照组同法注射等量PBS。4周时诱导心室颤动及进行心肺复苏。主要观察指标:移植后2,4周用超声心动图测量心功能;测量心肺复苏前及心肺复苏后4h内的血液动力学参数的变化;在心肺复苏72h后取心肌组织进行病理切片检查。结果:与模型对照组比较,移植后2,4周细胞移植组射血分数均明显升高(P<0.01)。在心肺复苏前及心肺复苏后4h内,与模型对照组比较,细胞移植组心脏指数、左心室收缩压力上升到40mmHg(1mmHg=0.133kPa)时的上升速率、左心室舒张速率、左心室舒张末压均有明显改善(P<0.01,P<0.05)。与模型对照组比较,细胞移植组大鼠心肺复苏后可生存至72h,生存时间明显延长(P<0.05)。病理切片结果显示心肌内存在大量PKH26标记的骨髓间充质干细胞。结论:大鼠心肌梗死后,骨髓间充质干细胞移植治疗能明显改善其心功能、心肺复苏前后的血流动力学参数以及生存时间。

BACKGROUND：The majority of published article on cardiopulmonary resuscitation（CPR） used healthy animals. In fact,patients commonly have severe heart diseases before CPR,leading to ventricular fibrillation. OBJECTIVE：To investigate outcome of myocardial function and cardiopulmonary resuscitation in myocardial infarction rats treated with bone marrow mesenchymal stem cells（MSCs） transplantation. DESIGN,TIME AND SETTING：A randomized,controlled animal experiment was performed at the University of Southern California and Second Hospital of Sun Yat-sen University from April to August 2007. MATERIALS：A total of 18 adult male SD rats were randomly divided into model control and cell transplantation groups with 9 animals in each group. In addition,1 SD rat aged 1 month was used to prepare bone marrow MSCs. METHODS：Myocardial ischemia was induced by ligation of the left anterior descending artery（LAD） . Animals respectively received 5×106 MSCs（0.1 mL） marked with PKH26 in phosphate buffer solution（PBS） or PBS alone 4 weeks after LAD ligation. Ventricular fibrillation and CPR were performed 4 weeks after MSCs or PBS injection. MAIN OUTCOME MEASURES：Heart function was evaluated by ultrasound cardiography 2,4 weeks after transplantation;hemodynamics was measured before and 4 hours following CPR. Myocardial tissues were harvested 72 hours after CPR for pathological exanimation. RESULTS：Compared with model control group,ejection fraction of transplantation group was significantly increased 2 and 4 weeks after transplantation（P 0.01） ,and cardiac index,dp/dt40,and-dp/dt were significantly improved before and within 4 hours after CPR（P 0.01,P 0.05） . Moreover,the rats survived longer in transplantation group（72 hours） after CPR compared with control group（P 0.05） . Pathological section results showed a large number of PKH26-labeled MSCs in the myocardium. CONCLUSION：Myocardial function,hemodynamics and survival time after CPR were significantly improved in animals treated with MSCs transplantation.