【摘要】 目的观察胞外信号调节激酶(extracellular signal regulated kinase 1/2,ERK1/2)抑制剂对11,12-环氧二十碳三烯酸(11,12-epoxyeicosatrienoic acid,11,12-EET)引起的结构型一氧化氮合酶(structural nitric oxide synthase,sNOS)变化的影响,了解NOS与ERK1/2在11,12-EET心脏保护中的作用方式。方法采用冠状动脉缺血60 min再灌注30 min的方法复制大鼠心肌缺血/再灌注模型。实验分为4组:缺血再灌注组(ischemia/reperfusion,I/R);假手术组(Sham);11,12-EET缺血再灌注组(EET+I/R);11,12-EET缺血再灌注加PD098059组(EET+I/R+PD)。观察缺血60 min再灌注30 min时心脏收缩期左心室内压上升的最大变化速率(+dp/dt max)及舒张期左心室内压下降的最大变化速率(-dp/dt max);采用化学比色法观察大鼠心肌组织sNOS活性。结果 I/R组的±dp/dtmax均低于Sham组及EET+I/R组(P<0.01);EET+I/R+PD组均低于EET+I/R组的±dp/dt max(P<0.01)。I/R组心肌sNOS低于Sham组(P<0.01)及EET+I/R组(P<0.01);EET+I/R组高于EET+I/R+PD组(P<0.01)。结论 11,12-EET对心功能的保护作用可能通过上调ERK进而增加sNOS的表达来实现。更多还原

【Abstract】 Objective To observe the effects of extracellular signal regulated kinase(ERK)1/2 inhibitor on the change of structural nitric oxide synthase(sNOS) caused by the 11,12-epoxyeicosatrienoic acid(1,2-EET) and study the mode of action of NOS and ERK in cardioprotection of 11,12-EET. Methods Myocardial ischemic/reperfusion model was produced by ligating the left anterior descending coronary artery for 60 min followed by 30 min reperfusion.The rats were divided into 4 groups: ischemia/reperfusion group(I/R);Sham group(Sham);EET and ischemia/reperfusion group(EET+I/R);EET,ischemia/reperfusion and PD098059 group(EET+I/R+PD).The heart function was evaluated by observing the maximum changes of intraventricular pressure(+dp/dt max and-dp/dt max).The activities of nitric oxide synthase of myocardium were examined by colorimetric method. Results At 30 min reperfusion,+dp/dt max and-dp/dt max decreased significantly in I/R group compared with Sham group and EET+IR group(P<0.01),and those in EET+I/R+PD group were less than those in EET+I/Rgroup(P<0.01).The activities of sNOS in IR group were lower than those in Sham group and EET+I/R group(P<0.01),and those in EET+I/R group were higher than those in EET+I/R+PD group(P<0.01). Conclusion Cardioprotective effect of 11,12-EET may be mediated by increasing the ERK then increasing the activity of sNOS.更多还原