11,12-环二十碳三烯酸对缺血/再灌注大鼠心肌一氧化氮合酶的影响

Effect of 11,12-Epoxyeicosatrienoic Acid on Nitric Oxide Synthase of Ischemia- reperfusion Myocardium in Rats

目的观察11,12-环二十碳三烯酸(11,12-EET)对缺血/再灌注大鼠心肌一氧化氮合酶(NOS)的影响。方法采用健康雄性Wistar大鼠制备心肌缺血/再灌注模型,实验分为5组:11,12-EET缺血/再灌注组(包括EET1、EET2、EET3)组,EET对照组,缺血/再灌注组,假手术组,正常对照组。观察缺血60min及再灌注30min两个时段心脏收缩期左心室内压上升的最大变化速率及舒张期左心室内压下降的最大变化速率;采用化学比色法观察大鼠心肌组织诱导型一氧化氮合酶(iNOS)及结构型一氧化氮合酶(cNOS)活性。结果缺血/再灌注组缺血60min及再灌注30min两个时段收缩期左心室内压上升的最大变化速率及舒张期左心室内压下降的最大变化速率均低于假手术组(P<0.01);EET1、EET2及EET3组均高于缺血/再灌注组(P<0.01)。缺血/再灌注组心肌cNOS低于假手术组(P<0.01),EET1、EET2及EET3组均高于假手术组(P<0.01)及缺血/再灌注组(P<0.01),EET2组高于EET对照组(P<0.01)。假手术组iNOS高于EET对照组(P<0.05),缺血/再灌注组高于假手术组(P<0.01);EET1、EET2及EET3组均低于缺血/再灌注组(P<0.01)。结论外源性11,12-EET改善缺血/再灌注心功能损伤同时出现cNOS增加及iNOS减少,提示11,12-EET拮抗缺血/再灌注损伤的作用可能与NOS同功酶改变有关。

Objective To observe the effect of 11,12-epoxyeicosatrienoic acid （11,12-EET） on nitric oxide synthase （NOS） in myocardial ischemia/reperfusion injury and explore the protective role of NOS in myocardium. Methods Rat myocardial ischemia/reperfusion model was produced by ischemia for 60 minutes and reperfusion for 30 minutes. Rats were divided into 5 groups： 11,12-EET ischemia/reperfusion groups （including EET1, EET2, and EET3 groups）, EET control group, ischemia/reperfusion group, sham operation group, and control group. Changes of the maximal rates of rise and decrease of left ventricular pressure （±dp/dtmax） were observed. Activities of inducible nitric oxide synthase （iNOS） and constrictive nitric oxide synthase （cNOS） in myocardium were measured with chemocolorimetry. Results During both ischemia period （60 min） and reperfusion period （30 min）, ±dp/dtmax was significantly lower in ischemia/reperfusion group than in sham operation group （P 〈 0.01）, and was significantly higher in EET1, EET2 and EET3 groups than in ischemia/reperfusion group （P 〈 0.01）.cNOS level was significantly lower in ischemia/reperfusion group than in sham operation group, was signifieantly higher in EET1, EET2 and EET3 groups than in sham operation group （P 〈 0.01）, and was signifieantly higher in EET2 group than in EET group （P 〈 0.01）. iNOS level was signifieantly higher in sham operation group than in EET eontrol group （P 〈 0.05）, was signifieantly higher in isehemia/ reperfusion group than in sham operation group （P 〈 0.01）, and was significantly lower in EET1, EET2 and EET3 groups than in ischemia/reperfusion ＇group （P〈0.01）. Conclusion Exogenous 11,12-EET can improve ischemia/reperfusion injury, which may be related with the changes of NOS isozymes.