卡托普利和低剂量阿司匹林相互作用对大鼠实验性心肌缺血及肝微粒体酶活性的影响  

Effects of interactions between captopril and low- dosage aspirin on experimental myocardial ischemia and the activity of liver microsomal enzymes in rats

作　　者：吕雄文[1] 陈卫东[1,2] 金涌 李常玉[1] 马传庚[1] 李俊[1] 

机构地区：[1]安徽医科大学药学系,临床药理研究所,合肥230032 [2]中国第十七冶金建设公司医院药剂科,马鞍山243000

出　　处：《中国药理学通报》2004年第1期104-109,共6页Chinese Pharmacological Bulletin

基　　金：安徽医科大学校科研资金资助课题 No 2 0 0 2 0 4

摘　　要：目的　观察卡托普利 (Cap)和低剂量阿司匹林 (Asp)相互作用对大鼠实验性心肌缺血及肝微粒体酶活性的影响。方法　建立异丙肾上腺素致大鼠实验性心肌缺血模型 ,采用正交设计给药方案 ,干式生化片测定LDH、CPK含量 ,同时观察心肌病理变化。采用差速离心法制备大鼠肝微粒体 ,测定细胞色素P4 5 0、b5含量及苯胺羟化酶活力。结果　Cap与低剂量Asp联用时对模型组血清中LDH、CPK水平存在明显的相互作用 ,且表现为拮抗效应。Cap显著减轻心肌组织病理损伤程度 ,而Asp对其无影响。Cap与Asp单用时对细胞色素P4 5 0含量无影响 ,但联用时较正常组及Asp单用组均显著增加。Asp降低细胞色素b5含量 ,联用Cap其含量明显增加。Cap单用时增加苯胺羟化酶活力 ,与Asp联用时活力进一步增加 ,而Asp本身对其无影响。 结论　低剂量Asp不减弱Cap对心肌组织病理损伤的保护作用 ,但二者联用对血清LDH、CPK的水平反而有促进作用 ,其机制可能与进一步诱导P4 5 0活性及苯胺羟化酶活力有关。AIM To observe the effects of interactions between captopril(Cap)and low dosage aspirin(Asp)on experimental myocardial ischemia and the activity of liver microsomal enzymes in rats. METHODS The myocardial ischemia model induced by isoproterenol was developed,the levels of lactate dehydrogenase (LDH), creatine phosphokinase(CPK)in serum and the changes of myocardial tissue were observed by orthogonal design.The liver microsomal fraction was prepared by differential centrifugation and the activity of liver microsomal enzymes P450, b5 and aniline hydroxylase in rats were studied. RESULTS The combination produced significant antagonistic interactions on the levels of LDH, CPK in serum. Cap reduced obviously the pathological grades of myocardial tissue,but Asp exerted no effect on it.The cytochrome P450 content was increased significantly when Cap and Asp combination was used compared to normal group and Asp alone.Asp alone significantly decreased the cytochrome b5 content,but it was increased significantly when in combination with Cap.Cap alone significantly induced the activity of aniline hydroxylase and their combination further increased it,but Asp itself had no effect on it. CONCLUSION The results suggeste that low dosage Asp does not attenuate the protective effects of Cap on the myocardial tissue injury,but their combination may produce adversed effects on the levels of LDH, CPK in serum. It may be related to their combination significantly induced the content of cytochrome P450 and the activity of aniline hydroxylase.

关 键 词：卡托普利 阿司匹林 正交设计 异丙肾上腺素 心肌缺血损伤 细胞色素P450类 苯胺羟化酶类 

分 类 号：R-332[医药卫生] R322.11