CD151激活PI3K/Akt/eNOS通路并促进小型猪缺血心肌血管生成  

rAAV-CD151 activates PI3K/Akt/eNOS pathway and promotes neovascularization in swine

作　　者：左后娟[1] 文莎[1] 刘正湘[1] 刘涛[1] 刘晓春[2] 刘毓[1] 林敬阳[1] 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,湖北武汉430030 [2]华中科技大学同济医学院,神经生物学系,湖北武汉430030

出　　处：《医学研究生学报》2009年第7期682-686,共5页Journal of Medical Postgraduates

基　　金：国家自然科学基金资助项目(批准号:3057072830670856)

摘　　要：目的:磷脂酰肌醇-3(羟基)激酶(PI3K)信号转导途径在生长因子促血管生成过程中起重要作用。四跨膜蛋白分子CD151如何参与PI3K信号转导途径尚不清楚。文中探讨重组腺相关病毒(rAAV)介导CD151转染心肌梗死小型猪模型对心肌血管生成的影响及机制。方法:结扎左冠状动脉左前降支建立小型猪心肌梗死模型,构建并包装绿色荧光蛋白、CD151、antiCD151重组腺相关病毒,分别注射至缺血心肌组织;同时设置正常对照组。8周后用vWF相关抗原免疫组化染色并计数注射部位心肌微血管数目,Western blot检测CD151及相关信号通路分子蛋白表达。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-反义CD151组(P<0.05)。rAAV-CD151组微血管密度[(30.20±2.35)个/视野]与正常对照组[(7.60±1.14)个/视野]、rAAV-GFP组[(14.40±1.34)个/视野]相比显著增加,rAAV-反义CD151组微血管密度[(7.20±1.30)个/视野]则明显低于其他手术组(P<0.05)。CD151表达增高促进了PI3K、p-Akt、p-eNOS的激活,促进NO的生成。结论:重组腺相关病毒携带CD151基因能有效转染心肌组织,明显增加微血管密度并激活PI3K/Akt/eNOS通路。Objective： The signal transduction pathway of phosphatidylinositol-3-kinase （PI3K） may play important roles in promoting angiogenesis induced by growth factors. The involvement of CD151, a member of transmember-4 superfamily, remains unclear. This study aimed to investigate the effects of the recombinant adeno-associated virus mediated CD151 （rAAV-CD151） gene delivery on capillary density in myocardial infarction swine and its mechanisms. Methods： We established the swine model of myocardial infarction by coronary artery ligation, and intramuscularly injected rAAV-CD151, rAAV-GFP and rAAV-antiCD151 into the ischemic myocardium. Eight weeks after coronary artery ligation, we detected the expression of CD151, and measured capillary density by immunostaining for the yon Willebrand factor. Results： Compared with the control and the rAAV-GFP groups, the rAAV-CD151 group showed a higher CD151 protein expression and capillary density in ischemic myocardium after myocardial infarction （P 〈 0.05 ）, while the rAAV-antiCD151 group exhibited a lower CD151 protein expression and capillary density （P 〈0.05）. In addition, CD151 activated PI3K, p-Akt and p-eNOS with an increased NO lev- el. Conclusion： rAAV-CD151 increases capillary density after myocardial infarction in swine. CD151 can transduce signals by up-regulating the PI3K/Akt/eNOS pathway.

关 键 词：CD151 心肌梗死 血管生成 

分 类 号：R338[医药卫生—人体生理学]