缺血-再灌注心肌诱导型一氧化氮合酶基因表达及其活性的变化和卡托普利的影响

目的探讨心肌诱导型一氧化氮合酶（iNOS）mRNA表达及其活性的变化在心肌再灌注损伤中的作用；研究卡托普利对缺血再灌注心肌保护作用的机制。方法采用Langendorff离体鼠心灌流模型；将18只SD大自鼠随机均分为3组：对照组、缺血一再灌组及卡托普利组；观察心肌iNOS mRNA表达及其活性、丙二醛（MDA）含量、过氧化物歧化酶（SOD）活性、肌酸激酶（CK）含量和冠状静脉流出液一氧化氮（NO）的变化。结果缺血再灌注后心肌iNOS mRNA表达显著上调（P〈0．001），iNOS活性增高（P〈0．001）；卡托普利组再灌注30min，心肌iNOS mRNA表达及其活性、心肌MDA含量均低于缺血-再灌组（P〈0．01，P〈0．05），而心肌SOD活性（P〈0．01）和CK含量（P〈0．05）高于缺血-再灌组，再灌注期间冠状静脉流出液NO含量高于缺血-再灌组（P〈0．01）。结论缺血-再灌注心肌iNOS基因表达上调，心肌iNOS活性增高；影响心肌iNOS mRNA表达、调节心肌iNOS活性可能是卡托普利抗心肌脂质过氧化作用的机制之一。

Changes of Myocardial iNOS mRNA Expression and iNOS Activity after Ischemia-Reperfusion and the Effect of Captopril

Objective To observe the alteration of myocardial inducible nitric oxide synthase (iNOS) 27 mRNA expression and iNOS activity after ischemia-reperfusion,and to evaluate the mechanism of cardioprotection of captopril on myocardial ischemia-reperfusion injury in rats. Methods The isolated Langendorff perfused rat heart model was established. Rat hearts were randomly divided into three groups(n=6 for each group): control group, ischemia-reperfusion(I/R) group and captopril group. Myocardial iNOS mRNA expression and iNOS activity, malondialdehyde(MDA) content, superoxide dismutase(SOD)activity, creatine phosphokinase(CK)content and also the changes of nitric oxide(NO) content in coronary effluent during reperfusion were observed. Results Myocardial iNOS mRNA expression was up-regulated significantly(P<0.001), and iNOS activity increased(P<0.001) after myocardial reperfusion in I/R group. In the captopril group lower myocardial iNOS mRNA expression(P<0.01), lower iNOS activity(P<0.01) and lower MDA content(P<0.05) were found, and higher myocardial SOD activity(P<0.01) and CK content(P<0.05) were found 30 min after reperfusion. NO content in coronary effluent in captopril group maintained at higher level(P<0.01) during reperfusion than that in the I/R group. Conclusion Myocardial iNOS mRNA expression was up-regulated and iNOS activity increased after myocardial ischemia-reperfusion. One of the mechanisms of captopril against lipid peroxidation might be attributed to its effect of limiting myocardial iNOS mRNA expression and regulating myocardial iNOS activity.