CD151转染心肌梗死小型猪减少心肌缺血面积并激活FAK／MAPK信号通路  

Through up - regulation FAK/MAPK pathway in a swine ischemia model, rAAV - CD151 reduced myocardial defect area

作　　者：左后娟[1] 刘涛[1] 刘正湘[1] 刘毓[1] 文莎[1] 刘晓春[2] 汪道文[1] 

机构地区：[1]华中科技大学同济医学院附属同济医院心内科 [2]华中科技大学同济医学院神经生物学系

出　　处：《中国急救医学》2009年第3期226-229,289,共5页Chinese Journal of Critical Care Medicine

基　　金：国家自然科学基金项目（No.30570728,No.30670856）

摘　　要：目的研究重组腺相关病毒介导CD151转染心肌梗死小型猪模型对心肌血运重建的影响及机制。方法结扎小型猪左冠状动脉前降支建立心肌梗死动物模型，分别注射CD151、antiCD151和GFP重组腺相关病毒至缺血心肌内，同时设置正常对照组。8周后13N—NH3 PET评价心肌血流灌注，Western blot检测CD151及相关信号通路分子蛋白的表达。结果术后8周，rAAV—CD151组心肌组织CD151蛋白表达明显高于正常对照组、rAAV—GFP组和rAAV—antiCD151组（P〈0．05）。rAAV—CD151组心肌缺血面积则明显低于rAAV—GFP组和rAAV—antiCD151组（P〈0．05）。CD151表达增高促进了FAK397、FAK925、ERK1／2和JNK的磷酸化激活。结论重组腺相关病毒携带CD151基因能有效转染心肌组织，明显减少心肌缺血面积，并激活FAK／MAPK通路。Objective To investigate the effect of the recombinant adeno - associated virus mediated CD151 （ rAAV - CD151 ） gene delivery on blood perfusion after myocardial infarction in swines and the mechanisms involved. Methods Swines receivicd coronary artery ligation and intramuscularly injection with rAAVs. 8 weeks after coronary artery ligation, the expression of CD151 was measured. 13N - NH3 PET was done to evaluate blood perfusion and western blot analysis was performed for mechanism. Results Compared to the control group and the rAAV - GFP group, the rAAV - CD151 group showed higher CD151 protein expression and reduced myocardial defect area, whereas the rAAV- antiCD151 group showed reversed changes. In addition, CD151 could up -regulate the FAK -MAPK pathway, including the activation of FAK, ERK and JNK. p38 MAPK may not involved in the CD151 signal transduction. Conclusion This study suggested that CD151 gene delivery improved blood perfusion. CD151 can transduce signals through up - regulating FAK - MAPK pathway.

关 键 词：CD151 心肌梗死 黏着斑激酶 

分 类 号：R542.22[医药卫生—心血管疾病]