氨基胍对阿霉素所致大鼠心肌毒性损伤的影响  

Effect of aminoguanidine on adriamycin induced cardiotoxic injury in rats

作　　者：阳冠明[1] 李树全[1] 叶司原 利基林 林善修[1] 

机构地区：[1]广西医科大学第一附属医院儿科,南宁530021 [2]广西肿瘤研究所生化室,南宁530021

出　　处：《中国药理学通报》2002年第5期552-555,共4页Chinese Pharmacological Bulletin

基　　金：广西自然科学基金 (No 982 40 0 1);广西教育厅科学基金 (No 1999 3 49)资助

摘　　要：目的　研究氨基胍 (AG)对阿霉素 (ADM )所致大鼠心肌毒性损伤的影响。方法　 32只Wistar大鼠随机分成 4组 :对照组 ;AG组 (AG 4 0 0 0mg·kg-1,ip ,隔日 1次 ,共 2 1次 ) ;ADM组 (ADM 2 5 0mg·kg 1,ip ,隔日 1次 ,共 6次 ) ;ADM +AG组 (ADM、AG的剂量及用法分别同ADM组、AG组 )。分别用血红蛋白氧化法、硝酸还原酶法测定心肌的一氧化氮合酶活性、一氧化氮 (NO)含量 ;用酶的速率法测定血清的肌酸激酶 (CK)及其同功酶CK MB活性、乳酸脱氢酶(LDH)及其同功酶LDH1活性 ;用光镜及透射电镜观察心肌的病理变化。结果　AG干预ADM处理的大鼠后 ,降低心肌的诱导型一氧化氮合酶 (iNOS)活性、NO含量、病变程度(P <0 0 1) ,降低血清的CK、CK MB、LDH、LDH1活性 (P <0 0 1)。AG、ADM对心肌的结构型一氧化氮合酶活性无影响 (P >0 0 5 )。AIM To study the effect of aminoguanidine (AG) on adriamycin(ADM) induced cardiotoxic injury in rats. METHODS Thirty two Wistar rats were randomly divided into four groups: control group; AG treated group (AG 400 0 mg·kg -1 ip every other day for 21 times ); ADM treated group (ADM 2 50 mg·kg -1 ip every other day for 6 times ); ADM with AG treated group( the dosage and method of ADM and AG were similar to ADM treated group and AG treated group, respectively). Hemoglobin oxidation method and nitrate reductase method were used to determine the activity of nitric oxide synthase, the content of nitric oxide(NO) in myocardium, respectively. Enzymic rate method were used to determine the activity of creatine kinase(CK) and its isoenzymic CK MB, the activity of lactic dehydrogenase(LDH) and its isoenzymic LDH 1 in serum. The pathological changes of myocardium were observed with light microscope and transmission electron microscope. RESULTS AG could significantly reduced the activity of inducible nitric oxide synthase (iNOS), the content of NO, the degree of pathological changes in myocardium ( P< 0 01) , significantly reduced the activity of CK, CK MB, LDH and LDH 1 in serum( P< 0 01), when ADM treated rats were intervened by AG. The AG and ADM have no effected on the activity of constitutive nitric oxide synthase in myocardium ( P> 0 05). CONCLUSION AG can selectively inhibit activity of iNOS in myocardium induced by ADM, reduce to produce NO in myocardium, thereby reduce injury of cardiotoxicity induced by ADM.

关 键 词：氨基胍 阿霉素 一氧化氮合酶 一氧化氮 心肌毒性损伤 抗肿瘤药物 动物实验 

分 类 号：R979.1[医药卫生—药品] R－322[医药卫生—药学]