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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 )。结论 AG选择性地抑制ADM所诱导心肌的iNOS活性使心肌产生NO减少而减轻ADM对心肌的毒性损伤
Objective To study the effect of aminoguanidine (AG) on myocardial toxicity induced by doxorubicin (ADM) in rats. Methods Thirty-two Wistar rats were randomly divided into 4 groups: control group, AG group (AG 40 000 mg · kg -1, ip every other day for 21 times), ADM group (ADM 250 mg · kg -1, ip, every other day, a total of 6 times); ADM + AG group (ADM, AG dose and usage were the same ADM group, AG group). The activity of nitric oxide synthase and the content of nitric oxide (NO) in myocardium were measured by hemoglobin oxidation method and nitrate reductase method respectively. Serum creatine kinase (CK) and isozyme CK MB activity , Lactate dehydrogenase (LDH) and its isoenzyme LDH1 activity. The pathological changes of myocardium were observed with light microscope and transmission electron microscope. Results After AG intervention, the iNOS activity, NO content and pathological changes (P <0.01) in the myocardium of ADM rats were decreased, and the activities of CK, CK MB, LDH and LDH1 were decreased (P <0 0 1). AG and ADM had no effect on the activity of structural nitric oxide synthase in myocardium (P> 0.05). CONCLUSION AG selectively inhibits the iNOS activity induced by ADM and decreases the production of NO in myocardium and decreases the toxic injury of ADM to myocardium