对硝基咖啡酸苯乙酯对ISO诱导的心肌损伤保护作用  

Cardioprotective effect of p-nitro caffeic acid phenethyl ester on isoproterenolinduced myocardial injury in rats

作　　者：游莉[1] 路晓钦[2] 董志[1] 

机构地区：[1]重庆医科大学药学院药理教研室,重庆400016 [2]重庆市第九人民医院药剂科,重庆400700

出　　处：《第三军医大学学报》2015年第20期2057-2061,共5页Journal of Third Military Medical University

摘　　要：目的研究咖啡酸苯乙酯衍生物对硝基咖啡酸苯乙酯(CAPE-NO2)对ISO诱导的心肌缺血的影响及其可能机制。方法利用简单随机化法将SD大鼠分成5组:空白对照组(Control组),药物对照组(CAPE-NO2组),模型对照组(ISO组),CAPE对照组(CAPE+ISO组),CAPE-NO2实验组(CAPE-NO2+ISO组)。CAPE(50μg/kg)和CAPE-NO2(50μg/kg)分别腹腔注射大鼠7 d后,皮下注射异丙肾上腺素(ISO)(85 mg/kg)诱导心肌损伤,用苯巴比妥钠(40 mg/kg)麻醉大鼠,检测心电图,处死大鼠,取心肌组织测定梗死面积和检测生化指标。结果 ISO诱导大鼠ST-段显著抬高(P>0.05),QRS段延长(P<0.05),梗死面积增大(P<0.01),抗氧化酶(SOD、CAT和GSH-Px)活性明显降低(P<0.01),NO产生增多(P<0.01)。与ISO组比较,CAPE和CAPE-NO2均能明显降低由ISO引起的ST段抬高(P<0.05,P<0.01)和QRS段延长(P<0.05),减少心肌梗死面积(P<0.05,P<0.01)和NO的产生(P<0.05,P<0.01),其中CAPE-NO2对大多数指标的影响比CAPE更显著。CAPE对ISO诱导的抗氧化酶活性降低无显著影响,而CAPE-NO2能够增加这些酶的活性。结论 CAPE-NO2对ISO诱导的大鼠心肌缺血损伤发挥保护作用优于CAPE,可能是通过提高抗氧化酶活性,阻止氧化应激和硝化应激的发生,减少心肌损伤。Objective To investigate the cardioprotective effect of p-nitro caffeic acid phenethyl ester （CAPE-NO2 ）, which is synthesized by coupling nitro group to CAPE, on isoproterenol （ISO）-induced myocardial infarction in rats and its underlying mechanisms. Methods Male Sprague-Dawley rats were randomly divided into 5 groups ： Control group, CAPE-NO2 group, ISO group, CAPE ＋ ISO group and CAPE- NO2 ＋ ISO group. CAPE （50 μg/kg） and CAPE-NO2（50 μg/kg） were injected intraperitoneally into the rats for 7 d, and then the rats were administered with ISO （85 mg/kg） subcutaneously to induce myocardial injury. After that, the rats were anaesthetized with pentobarbital sodium （40 mg/kg ） to record electrocardiogram, and then sacrificed to detect the infarct size and biochemical indexes of the heart tissues. Results The rats treated with ISO showed marked elevation in ST-segment （P 〉 0. 05 ） , enlargement in QRS duration （P 〈0. 05）, significant increase in the infarct size （P 〈0. 01 ） and NO content （P 〈0. 01 ）, and significant decrease in the activities of endogenous antioxidants （SOD, CAT and GSH-Px） （P 〈 0. 01 ）. Compared with the ISO group, both the CAPE ＋ ISO group and the CAPE-NO2 ＋ ISO group could significantly reduce the elevation of ST-segment （ P 〈 0. 05 and P 〈 0. 01 ）, enlargement of QRS duration （ P 〈 0. 05 ）,infarct size （P 〈 0. 05 and P 〈 0. 01 ） and NO content （ P 〈 0. 05 and P 〈 0. 01 ）, however, the effect of CAPE-NO2 was more significant than that of CAPE. CAPE had no effect on the antioxidants, but the administration of CAPE-NO2 resulted in significant rise of the antioxidants activities. Conclusion The cardioprotective effect of CAPE-NO2 on ISO-induced myocardial infarction is better than that of CAPE in the rats. The mechanism might be associated with the elevation of antioxidant activity to inhibit oxidative stress and nitrative stress.

关 键 词：对硝基咖啡酸苯乙酯 心肌损伤 抗氧化 

分 类 号：R-332[医药卫生] R542.05