阿霉素致大鼠心脏氧化损伤及其机制的研究

Experimental study on adriamycin-induced cardiotoxicity in rats

目的观察不同剂量阿霉素(ADR)给药后不同时间对大鼠心脏的作用,探讨ADR心脏毒性损伤的可能作用机制。方法60只大鼠随机分为对照组和3个给药组。给药组分别单次腹腔注射5、10和20 mg/kg的ADR溶液;对照组给予生理盐水。给药后第1、2和4天每组分别处死5只动物,取心室制备组织匀浆,用硫代巴比妥酸法(TBA)测定丙二醛(MDA)含量,二硫代双硝基苯甲酸法(DTNB)测定总巯基(TSH)和非蛋白巯基(NPSH)含量,Griess试剂法测定一氧化氮(NO)含量。结果随着剂量的增加,给药后第1天心脏组织中NPSH、TSH含量增加;给药后第2天TSH、NO含量增加;给药后第4天MDA、NO含量增加,NPSH含量降低;与对照组比较,20 mg/kg组差异有显著性(P<0.05,P<0.01)。结论阿霉素致心脏损伤的机制可能与心脏组织中NPSH的耗竭及NO产生过多有关。

Objective To investigate adriamycin（ADR） induced cardiotoxicity with different dosage after different exposure times so as to study the potential mechanisms of carditoxicity induced by ADR in rats. Methods 60 Wistar rats were randomly divided into 4 groups：control group;three ADR treated groups（ADR 5, 10,20 mg/kg; ip respectively）. The content of nitric oxide（NO） and malondialdehyde（MDA）, total sulthydryl（TSH） and non-protein sulthydryl（NPSH） in hearts were measured respectively at d 1,2,4. Results NPSH markedly increased in dose-dependent manner at d 1 after treatment,but markedly decreased at d 4 after treatment;TSH markedly increased in dose-dependent manner at d 1 and 2 after treatment; NO markedly increased in dose-dependent manner at d 2 and 4 after treatment ; and MDA markedly increased in dose-dependent manner at d 4 after treatment. Conclusion The mechanisms of ADR induced cardiotoxicity may related with ADR decrease the level of antioxidate and increase the content of NO.