依那普利改善心梗后微环境提高人脐血间充质干细胞静脉移植疗效的研究

目的本研究假没依邪普利可增强脐血间充质干细胞移植治疗急性心肌梗死的疗效。研究此协同作用与减少心梗后TNF—α的表达，减少心梗后MDA含量、增强SOD活性，拮抗心梗后局部微环境的氧化应激反应有关。方法建造家兔急性心肌梗死模型后，随机分为：A：空白对照细；B：心肌梗死对照组；C：人脐血间充质干细胞移植组；D：依那普利治疗组；E：依那普利＋人脐血间充质干细胞移植组。心梗术后A、B、C组立即予以生理盐水2ml／kg灌胃．D、E组以依那普利2mg／kg灌胃，同时c、E组于术后第7灭经耳缘静脉注射含人脐血间充质1：细胞3×10。／500rB。的生理盐水至术后2周，而A、B，D组同时间予以相同剂最的生理盐水静脉给药。分别于术后、细胞移植后1周、细胞移植后2周，超声心动图检测箨组家兔的心功能情况。细胞移植后2周，免疫组化及RTPCR法检测心肌中TNF-α的表达，分别检测各组MDA含量、SOD活忱及ACE活性情况。结果依那酱利干预后，人脐血间充质干细胞移植能够更明盟的改善心梗后心功能指标LVEF和LVFS（P〈0．05）。依那瞥利治疗可减少心梗后心肌组织中TNF-α表达（P〈0．05）。依那普利联合人脐血间充质干细胞移植，比单纯的人脐血间充质干细胞移植更能够减少心肌组织中TNF-α表达（P〈0．05）。依那普利联合人脐血间充质干细胞移植，比单纯的人脐血间充质干细胞移植更能够减少心梗后MDA含摄、增强SOD活性（P〈0．05）。依那辫利联合人脐血间充质干细胞移植，比单纯的人脐血间充质干细胞移植和单纯依那普利治疗更能够减少心梗后的ACE活性（P〈0．05）。结论依那普利对心梗后局部微环境的氧化应激及炎症反应的干预作用，可增强人脐血间充质干细胞移植后抑制炎症因子TNF-α的分泌及表达的能力，增强人脐血间充质干细胞移植减少MDA含蜒、增强SOD活性的能力，提高人脐血间充质干细胞静脉移植改善心功能指标LVEF和LVFS的能力，可能与抑制ACE活性有关。

Objective Inflammation, oxidative stress are the main characters in the myocardial micro-environment after AMI. In flammation and oxidative stress play an important role in cardiac remodeling post-MI. We hypothesize that Enalapril might enhances therapeutic efficacy on AMI with transplantation of hUCMSCs via inhibition of inflammation and oxidative stress in the myocardial mi cro environment after AMI. Methods and Results Human umbilical cord blood mesenchymal stem cells were injected intravenously to the rabbits underwent myocardial infarction with previously intragastric administration of Enalapril. There were two other groups that received either stem cells transplantation or Enalapril alone. Cardiac functions were assessed by echocardiography. Expression of inflam matory factor TNF-α were assessed by Immunohistochemical methods and real time PCR, Oxidative stress was reflected by content of MDA and SOD activity. Results The indicated that combination of Enalapril and transplantation of hUCMSCs showed significantly benefits in preservation of cardiac functions. Compared with stem cells transplantation or Enalapril alone, the combination treatment al- so showed a significant decrease in the level of the pro inflammatory TNF-α, content of MDA and ACE activity, and a market increase in SOD activity in the infracted myocardium. Conclusion Combination of Enalapril and transplantation of hUCMSCs markedly increased cardiac function, beneficially influenced inflammation and oxidative stress after acute myocardial infarction. It maybe related with inhibi- ting ACE activity in the infracted myocardium via Enalapril.