曲美他嗪改善骨髓间质干细胞在大鼠体外缺氧模型和体内心肌梗死模型中的存活和分化作用  

Improvement of Trimetazidine on Viability of Bone Marrow Mesenchymal Stem Cells of In Vitro Hypoxia Model and In Vivo Myocardial Infarction Model in Rats

作　　者：朱刚艳[1] 徐红新[2] 田毅浩[3] 马红梅[1] 唐世琪[1] 汪福良[1] 邬松林[1] 

机构地区：[1]武汉大学人民医院老年病科,湖北省武汉市430060 [2]武汉大学人民医院心内科,湖北省武汉市430060 [3]武汉大学基础医学院解剖教研室

出　　处：《中国循环杂志》2011年第5期386-389,共4页Chinese Circulation Journal

基　　金：国家自然科学基金资助课题(编号:30700314);湖北省武汉市科技局课题(编号:20065004116-02)

摘　　要：目的:探讨曲美他嗪能否改善骨髓间质干细胞(MSCs)在体外缺氧模型及体内急性心肌梗死(AMI)大鼠心脏的存活和分化。方法:加入或未加入曲美他嗪的MSCs在无血清培养基培养并缺氧暴露12 h,采用透射电子显微镜和流式细胞仪检查第3代MSCs的活力和凋亡。30只Wistar大鼠随机分为3组(各组n=10),AMI对照组、MSCs组及MSCs+曲美他嗪组。结扎左冠状动脉前降支制备AMI模型。将MSCs(细胞数4×107)注入梗死心肌边缘(MSCs组和MSCs+曲美他嗪组)。MSCs+曲美他嗪组的大鼠在AMI前3 d开始至AMI后28 d加喂曲美他嗪,剂量2.08 mg/(kg.day)。AMI对照组动物注射无血清培养基。移植28 d后,超声心动图评估心脏结构和功能。免疫荧光染色检测移植细胞在体内的存活和分化。原位末端标记(TUNEL)法检测梗死周围区域的细胞凋亡。结果:缺氧培养下,MSCs+曲美他嗪组的MSCs细胞凋亡降低了一半。在体内,与AMI对照组相比,MSCs组和MSCs+曲美他嗪组的心肌梗死面积显著缩小,心功能明显改善。与MSCs组相比,MSCs+曲美他嗪组治疗表现出更低的干细胞凋亡,更高的干细胞存活,更小的心肌梗死面积,与进一步改善的心功能。结论:联合曲美他嗪的MSCs移植治疗,在MSCs的存活和心脏功能的恢复方面优于单纯MSCs移植。Objective ：To investigate the improvement of trimetazidine （TMZ） on viability of bone marrow mesenchymal stem cells （MSCs） in an in vitro model of hypoxia culture and in vivo model of acute myocardial infarction （AMI） in rats. Methods：In vitro：Rats＇ MSCs were cultured in serum-free medium and exposed to hypoxia condition, and then examined at the third passage for their viability and apoptosis by transmission electron microscopy and flow cytometry. In vivo：AMI model was created by coronary artery ligation. 30 Wista rats were randomly divided into 3 groups ,n= 10 in each group. AMI control gruup ,the serum-free medium was injected ; MSCs alone group, MSCs （4 × 10^7 cells） were injected into the borderline of infarcted myocardium and MSCs＋TMZ group,the rats were fed with TMZ 2. 08mg/（ kg · day） from 3 days before AMI to 28 days after AMI. Cardiac structure and tunction were assessed by echocardiography 28 days after MSCs implantation. The viability and apoptosis of implanted MSCs were detected at the borderline of infarcted myocardium. Results：In vitro ：TMZ-treated MSCs presented half amount lower apoptosis rate than those without TMZ-treated MSCs under hy- poxia culture. In vivo：Compared with AMI control group, the myocardial infarction sizes were significantly smaller in MSCs alone group and in MSCs＋TMZ group,the cardiac function was significantly improved. Compared with MSCs alone group, MSCs had thehigher viability and lower apoptosis,had the smaller size of infarction and the better cardiac function in MSCs ＋ TMZ group. Conclusion：The combination of MSCs with TMZ implantation is superior to MSCs alone for higher MSCs viability and better cardiac function recovery in AMI model in rats.

关 键 词：曲美他嗪 骨髓间质干细胞 移植 急性心肌梗死 

分 类 号：R541[医药卫生—心血管疾病]