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目的观察苯那普利、厄贝沙坦对慢性心力衰竭(CHF)大鼠主动脉内皮氧化应激以及一氧化氮合酶(NOS)、还原型辅酶Ⅱ(NADPH)氧化酶重要亚单位p22phox蛋白表达的影响。方法采用大鼠腹主动脉缩窄法造成压力负荷性心肌肥厚致心力衰竭模型。分为5组:假手术组、未治疗组、苯那普利组、厄贝沙坦组及联合用药组。每2周测定大鼠尾动脉血压,8周后检测心功能指标及电镜观察主动脉的病理超微结构,同时采用黄嘌呤氧化酶法检测血清超氧化物歧化酶(SOD)活性,硫代巴比妥酸法测定丙二醛与硝酸还原法检测一氧化氮水平,采用匀相竞争放射免疫法测定血浆血管紧张素Ⅱ(AngⅡ)和环磷酸鸟苷(cGMP)含量,蛋白质印迹检测主动脉内皮组织NOS与NADPH氧化酶亚单位p22phox的蛋白表达。结果用药3组的主动脉病变明显减轻,内皮细胞较完整,丙二醛、左室舒张末压(LVEDP)、诱导型一氧化氮酶(iNOS)、p22phox蛋白表达均低于未治疗组(均P<0.01),且联合组比单用组低(P<0.05);一氧化氮、SOD、cGMP、左室收缩压(LVSP)、室内压最大上升速率(dp/dtmax)、室内压最大下降速率(-dp/dtmax)、内皮型一氧化氮合酶(eNOS)表达显著高于未治疗组(均P<0.05),其中联合组SOD水平比厄贝沙坦组高(P<0.05);苯那普利组血浆AngⅡ含量低于未治疗组,而联合组低于单用组(均P<0.01);整个实验过程中各治疗组之间血压无差异。结论苯那普利和厄贝沙坦单用均能改善CHF大鼠动脉内皮细胞结构及氧化应激状态,联合应用具有协同作用。
Objective To observe the effects of benazepril and irbesartan on the oxidative stress in the aorta and the expression of nitric oxide synthase (NOS) and p22phox protein, an important subunit of NADPH oxidase in chronic heart failure rats. The impact of expression. Methods A rat model of heart failure caused by pressure overload myocardial hypertrophy was induced by abdominal aorta constriction in rats. Divided into 5 groups: sham operation group, untreated group, benazepril group, irbesartan group and combination group. The tail arterial pressure was measured every 2 weeks, 8 weeks later, the indexes of cardiac function and pathological ultrastructure of the aorta were observed by electron microscopy. The activities of superoxide dismutase (SOD), thiopental The levels of NO and nitric acid were measured by the method of titration and the levels of nitric oxide were determined by the method of homogenous competition radioimmunoassay. The contents of plasma angiotensin Ⅱ (cGMP) and plasma angiotensin Ⅱ (cGMP) Tissue NOS and NADPH oxidase subunit p22phox protein expression. Results The aortic lesions of the three groups were significantly alleviated and the endothelial cells were relatively intact. The expressions of malondialdehyde, left ventricular end-diastolic pressure (LVEDP), inducible nitric oxide synthase (iNOS) and p22phox protein were lower than those in the untreated group (P <0.01), and the combined group was lower than the single group (P <0.05); the nitric oxide, SOD, cGMP, LVSP, dp / dtmax, (-dp / dtmax) and eNOS expression were significantly higher in untreated group than those in untreated group (all P <0.05). The SOD level in combination group was higher than that in irbesartan group (P <0.05). The blood levels of AngⅡ in benazepril group were lower than those in untreated group and those in combined group were lower than those in single group (all P <0.01). There was no difference in blood pressure between treatment groups during the whole experiment. Conclusion Both benazepril and irbesartan alone can improve the arterial endothelial cell structure and oxidative stress in CHF rats, and synergistic effect may be obtained when combined with benazepril and irbesartan.