卡托普利对缺血-再灌注鼠心肌一氧化氮及其合酶活性的影响

目的　研究一氧化氮 (NO)和一氧化氮合酶 (NOS)在心肌再灌注损伤中的作用 ,探讨卡托普利(captopril)对缺血 -再灌注鼠心肌保护的机制。　方法　采用 L angendorff离体鼠心灌流模型 ,将 18只 SD大白鼠随机分为 3组 (每组 6只 ) ,对照组、缺血 -再灌注组、卡托普利组。观察心肌 NOS同工酶活性、过氧化物歧化酶活性、丙二醛含量、肌酸激酶含量和冠脉流出液 NO的变化。　结果　缺血 -再灌注组与对照组比较心肌诱导型 NOS(i NOS)活性增高 (P<0 .0 0 1) ,而心肌原生型 NOS(c NOS)活性及总 NOS活性显著降低 (P<0 .0 0 1,0 .0 5 ) ,冠脉流出液 NO含量下降(P<0 .0 1)。卡托普利组再灌注 30分钟 ,心肌 i NOS活性低于缺血 -再灌注组 (P<0 .0 1) ,c NOS活性和总 NOS活性高于缺血 -再灌注组 (P<0 .0 1,0 .0 5 ) ,再灌注期间冠脉流出液 NO水平高于缺血 -再灌注组 (P<0 .0 1) ,心肌损伤较缺血 -再灌注组减轻。　结论　心肌 NOS同工酶活性及 NO产生的失常是心肌再灌注损伤的重要机制之一 ,卡托普利可通过调节心肌 NOS同工酶活性 ,维持正常的 NO水平 ,起到心肌保护作用。

Effect of Captopril on Nitric Oxide and Its Synthase Activity During Myocardial Ischemia-reperfusion in Rat Heart

ObjectiveTo study the effect of myocardial nitric oxide (NO) and nitric oxide synthase (NOS) in myocardial ischemia-reperfusion injury and evaluate the mechanism of cardioprotection of captopril on myocardial ischemia-reperfusion injury in rat heart. MethodsThe isolated Langendorff perfused rat heart model was used. Rat hearts were randomly divided into three groups (6 in each group): control group, ischemia-reperfusion (I/R) group and captopril group. NOS isoenzyme activity, superoxide dismutase(SOD) activity, malondialdehyde(MDA) content, creatine phosphokinase(CK)content and the changes of NO content in coronary effluent during reperfusion were observed.ResultsMyocardial inducible NOS (iNOS) activity in I/R group was increased than that of control group, however myocardial constitutive NOS(cNOS) activity and total NOS activity decreased significantly (P<0.001,0.05)after myocardial reperfusion and NO content in coronary effluent reduced (P<0.01) in I/R group. Captopril group presented lower myocardial iNOS activity (P<0.01) and higher cNOS and total NOS activity (P<0.01,0.05) 30 min after reperfusion. NO content in coronary effluent in captopril group maintained higher level (P<0.01) during reperfusion, these were compared with I/R group .And myocardial injury in captopril group was ameliorated. ConclusionsThe abnormality of myocardial NOS isoenzyme activity and NO production may be one of the important factors inducing myocardial I/R injury.The myocardial protection mechanism of captopril may be attributed to its effect on maintaining normal NO level by regulating myocardial NOS isoenzyme activity.