p38MAPK抑制剂联合MSC移植治疗大鼠心肌梗死的实验研究  

Inhibition of p38MAPK potentiates mesenchymal stem cell therapy against myocardial infarction injury in rats

作　　者：章志玲[1] 张明[1] 周淑兰[1] 梅志亮[1] ZHANG Zhi-ling;ZHANG Ming;ZHOU Shu-lan;MEI Zhi-Hang(The Second Department of Cardiovascular Medicine,Jiangxi Provincial People's Hospital, Jiangxi 330006, Nanchang, China)

机构地区：[1]江西省人民医院二部心内科

出　　处：《广东医学》2019年第15期2135-2138,共4页Guangdong Medical Journal

基　　金：江西省卫生计生委科技计划项目(编号:20175011)

摘　　要：目的旨在探讨间充质干细胞(mesenchymal stem cell,MSC)联合p38MAPK抑制剂增强大鼠心肌梗死损伤的保护作用,并揭示其作用机制。方法采用左冠状动脉前降支结扎法建立心肌梗死模型。采用ST段抬高和病理改变对模型进行评价。模型建立后,将大鼠随机分为4组。MSC移植组、p38MAPK抑制剂(SB203580)组、MSC+SB203580组和模型对照组。MSC和SB203580每周注射2次,连续4周。应用HE染色和Tunel法评价病理变化及细胞凋亡。通过实时PCR和Western blot检测p38MAPK和TAK1的表达。结果 HE染色显示,模型大鼠典型损伤包括不规则细胞排列、炎症浸润,MSC治疗或p38MAPK抑制剂能改善病理变化。其中,MSCs联合p38MAPK抑制剂的效果最佳。Tunel法检测表明,与单用MSC或p38MAPK抑制剂相比,MSC联合应用p38MAPK抑制剂有明显增强作用。MSC与p38MAPK抑制剂的联合应用降低了TAK1和p38MAPK的表达。结论 p38MAPK抑制剂增强MSCs对大鼠心肌梗死的保护作用。Objective To investigate the protective effect of mesenchymal stem cell(MSC) therapy associated with p38MAPK inhibition against myocardial infarction injury in rats and also to disclose tis mechanisms. Methods Myocardial infarction model was established by ligation of anterior descending branch of left coronary artery. The rats were divided into four groups: MSCs transplantation, p38MAPK inhibitor(SB203580), MSC+ SB203580 and model control groups. HE staining was applied to evaluate pathological changes. The expressions of p38MAPK and TAK1 were detected by real-time PCR and Western blot. Results The model was successfully established with ST elevation and pathological changes. After modeling, the rats were randomly divided into four groups. As shown by HE staining, classical injury, including irregular cell arrangement, inflammation infiltrations were observed in modeled rats, while MSCs therapy or p38MAPK injection ameliorated the pathological changes. Interestingly, the associated application of MSCs with p38MAPK injection exerted the optimal effect. Tunnel assay showed that the associated application of MSCs with p38MAPK also showed potentiated effects compared with single MSCs therapy or p38MAPK injection. The associated application of MSCs with p38MAPK inhibition down-regulated TAK1 and p38MAPK in both mRNA and protein levels. Conclusion p38MAPK inhibition potentiates the protection of MSCs therapy against myocardial infarction in rats.

关 键 词：P38MAPK 间充质干细胞 心肌梗死 

分 类 号：R542.22[医药卫生—心血管疾病] R541.4[医药卫生—内科学]