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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。
PURPOSE: eNOS and NO play an important role in reducing cardiac remodeling and apoptosis after myocardial infarction. However, the anti-inflammatory effect of eNOS and the role of MAPK in eNOS / NO-mediated cardiac remodeling remain unclear. Methods: The Wistar rats were divided into 24 h and 7 d groups. The effects of eNOS gene transfection on inflammation, signal pathway protein expression, cardiac function and ventricular remodeling were observed. Four days prior to myocardial infarction, local eNOS gene transfection was performed by cardiac surface injection. The eNOS gene transfection was observed by immunohistochemistry and NO production. Cardiac artery function was measured by carotid artery cannulation. Masson staining was used to detect myocardial infarction area The expression of ED-1 was detected by immunohistochemistry to observe the inflammation. Western blotting was used to detect the effect of eNOS gene transfection on the protein expression of MAPKs signal pathway in myocardium. Results: Compared with the MI control group and the Ad.Null group, the eNOS expression was significantly increased and the NO production was significantly increased after eNOS gene transfection ([(0.42 ± 0.09) vs (0.16 ± 0.05) nmol / mg, n = 7, P <0.01]. Compared with MI group and Ad.Null group, eNOS gene transfection could significantly reduce the expression of ED-1 after myocardial infarction. The area of myocardial infarction was (22.5 ± 2.8%) vs (46.4 ± 2.9%) or (43.5 ± 3.3% , n = 7, P <0.01], cardiac function improved significantly. P38MAPK, JNK expression was significantly reduced. CONCLUSION: Compared with other experimental groups, the inflammation induced by myocardial infarction after eNOS gene transfection is significantly reduced, the area of myocardial infarction is significantly reduced, and the cardiac function is obviously improved. The protective effect of eNOS gene on the heart may be related to the inhibition of the expression of P38MAPK and JNK. This cardioprotective effect of eNOS can be blocked by L-NAME.