MAPK在eNOS基因转染对心肌梗死后心脏保护中的作用  

The role of MAPK in the cardioprotective effects of eNOS gene transfection after myocardial infarction

作　　者：陈磊磊[1] 尹航[1] 黄峻[1] 王连生[1] 杨志健[1] 曹克将[1] 朱铁兵[1] 

机构地区：[1]南京医科大学第一附属医院心内科,江苏南京210029

出　　处：《南京医科大学学报（自然科学版）》2009年第12期1643-1647,共5页Journal of Nanjing Medical University(Natural Sciences)

基　　金：国家自然科学基金资助(30370575)

摘　　要：目的:eNOS及NO在心肌梗死后减轻心脏重塑和细胞凋亡方面发挥着重要作用,然而,eNOS的抗炎作用、MAPK在eNOS/NO介导的心脏重塑作用仍不清楚。方法:采用Wistar大鼠,实验分为24h组和7天组,分别观察eNOS基因转染对心肌梗死后炎症、信号通道蛋白表达、心脏功能和心室重塑的影响。心肌梗死前4天通过心脏表面注射进行局部eNOS基因转染,通过免疫组化和测定NO的产量观察eNOS基因的转染情况;采用颈动脉插管法测定心脏功能;采用Masson染色检测心肌梗死面积;免疫组化检测ED-1表达观察炎症情况。采用Westernblot法检测eNOS基因转染对心肌MAPKs信号通道蛋白表达的影响。结果:研究发现eNOS基因转染后,eNOS表达明显增加,NO生成明显提高,与MI对照组及Ad.Null组比较[(0.42±0.09)vs(0.18±0.06)or(0.16±0.05)nmol/mg,n=7,P<0.01]。与MI组及Ad.Null组比较,eNOS基因转染能明显减少心肌梗死后ED-1的表达、心肌梗死面积[(22.5±2.8%)vs(46.4±2.9%)or(43.5±3.3%),n=7,P<0.01],心脏功能明显改善。P38MAPK、JNK表达明显减少。结论:与其他实验组比较,eNOS基因转染后心肌梗死导致的炎症明显减轻、心肌梗死面积明显减少、心脏功能明显改善,eNOS基因对心脏的保护作用可能与抑制P38MAPK、JNK的表达有关。eNOS的这种心脏保护作用可以被L-NAME所阻断。Objective：Endothelial nitric oxide synthase（eNOS）and nitric oxide（NO）have been implicated to protect myocardial ischemia injury. However,the angiogenic effect of eNOS in infarcted myocardium and the role of MAPK signaling in eNOS/NO-mediated cardiac remodeling have not yet been elucidated. We observed the cardioprotective effects of eNOS gene transfection after myocardial infarction. Methods：Wistar rats（male） were divided into short-term group（24-hour infarction） for signaling investigations and long-term group（7-day infarction） for ventricular remodeling. Human eNOS gene in an adenovirus vector was delivered locally into rat heart 4 days prior to induction of myocardial infarction（MI） by left anterior descending coronary artery ligation. Cardiomyocyte inflammation was detected by immunohistochemistry. Expression of MAPKs were detected by Western Blot. Results：eNOS gene transfection significantly reduced myocardial infarct size and improved cardiac contractility as well as left ventricle （LV） diastolic function after MI. In addition, eNOS significantly reduced MI-induced cardiomyocyte inflammation. Activation of JNK and P38 after MI were also dramatically reduced by eNOS. Moreover,the deterioration of both systolic and diastolic function in conjunction with thin LV remodeling after MI were prevented by eNOS. Conclusion：These results demonstrate that the eNOS / NO system provides cardiac protection after MI injury through inhibition of cardiac inflammation and suppression of JNK and P38 signaling. The resule that all the cardioprotective effects of eNOS were blocked by N（ω）-nitro-L-arginine methyl ester administration indicates a NO-mediated event.

关 键 词：内皮型一氧化氮合酶 心肌梗死 心脏重塑 丝裂原活化蛋白激酶 

分 类 号：R542.22[医药卫生—心血管疾病]