福辛普利预处理对大鼠缺血再灌注心肌的保护作用

Effect of Pretreatment with Fosinopril on Activity of Superoxide Dismutase and Level of Malondialdehyde in Ischemia-reperfusion Myocardium

目的研究福辛普利预处理对大鼠缺血再灌注心肌过氧化损伤的保护作用。方法将成年大鼠随机分成正常对照组、缺血再灌注(IR)组、福辛普利预处理组、缓激肽B2受体拮抗剂Hoe140加福辛普利组,麻醉大鼠冠脉结扎30min后,再灌60min,观察各组缺血再灌注前后心功能及超氧化物歧化酶(SOD)活性和丙二醛(MDA)含量的变化。结果各组大鼠心肌组织超氧化物歧化酶活性比较:缺血再灌注组大鼠心肌组织中超氧化物歧化酶活性显著低于假手术组(3.68±1.35,4.83±1.33)ukat/g(P<0.05),福辛普利预处理10mg/(kg.d)组均显著高于缺血再灌注组4.49±1.44ukat/g(P<0.05)。各组大鼠心肌组织丙二醛含量比较:缺血再灌注组大鼠心肌组织中丙二醛含量显著高于假手术组(6.77±4.38,3.86±1.76)nmol/g(P<0.05),福辛普利预处理组均显著低于缺血再灌注组(2.73±1.99)nmol/g(P<0.05)。结论福辛普利预处理能通过增强心肌抗氧化酶的活性,抵制脂质过氧化反应,减轻自由基损害,对缺血再灌注心肌产生保护作用。福辛普利产生的药理性预适应作用至少部分通过减少AngⅡ的生成而激活缓激肽而发挥作用。

Objective To analyse the protective effect of pretreatment with fosinopril ischemic - reperfusion myocardium with peroxidative injury. Methods Sixty adult WISTAR rats were randomly divided into four groups：normal matched control,ischemia/reperfusion（IR） , fosinopril preconditioning（IP）, and bradykinin BE receptor antagonist Hoe140 ＋ fosinopril. The myocardial ischemiz was produced by coronary artery ligation for 30 min followed by reperfusion 60 min, myocardial superoxide dismutase（SOD） activity and malondialdehyde （MDA） were determined, and the assessment of heart function was performed. Results （1） Comparison in SOD activity of myocardium among each groups： that in the ischemic reperfusion group was obviously lower than the sham - operation group （3.68 ± 1.35,4. 83 ± 1.33 ） ukat/g（ P 〈 0.05 ）, while it was significantly higher in fosinopril group than the ischemic reperfusion （4.49 ± 1.44 ） ukat/g （ P 〈 0.05 ）. （2） Comparison in level of MDA in myocardium among each groups： it was markedly higher in the ischemic reperfusion group than the sham -operation group（ 6.77 ± 4.38,3.86 ± 1.76 ）nmol/g （P 〈 0. 05 ）, while it was markedly lower in fosinopril group than the ischemic reperfusion （2. 73 ± 1.99）nmol/g（ P 〈 0. 05 ）. The cardioprotective effect was significantly attenuated when the bradykinin BE receptor antagonist Hoe140 were injected prior to fosinopril. Conclusion Fosinopril pretreatment can protect the ischemia -reperfusion myocardium by enhancing the activity of auti -oxidative enzyme, inhibiting lipid peroxidation and attenuating the oxygen free radicals - mediated damage to the myocardium. There are protective effects of Fosino- pril on ischemiareperfusion myocardium. The myocardial ischemia reperfusion injury protection mechanism of fosinopril is most likely to be mediated by bradykinino