目的 研究应用阿霉素制备急性心脏毒性大鼠模型的最佳给药方案。方法 雄性Wistar大鼠45只，分别编号并随机分为对照组（n=12）、模型组1（n=20）和模型组2（n=13）。模型组1大鼠按2.5 mg·kg^-1 ip阿霉素，每2天1次，持续16 d，累积剂量为20 mg·kg^-1，考察累积剂量为15、20 mg·kg^-1时的药效学指标；模型组2大鼠按5.0 mg·kg^-1 ip阿霉素，每2天1次，持续10 d，累积剂量为25 mg·kg^-1，考察累积剂量为15、20、25 mg·kg^-1时药效学指标；对照组大鼠给予与模型组1同等剂量的生理盐水，每2天1次，持续16 d。观察各组大鼠的一般状态、死亡率、超声心动图、心脏指数以及血清中肌酸激酶（CK）、肌酸激酶同工酶（CK-MB）、乳酸脱氢酶（LDH）水平。结果 与对照组比较，模型组1大鼠第6、8、10、12、14、16天体质量显著下降（P<0.05、0.01）；模型组2第4、6、8、10天体质量显著下降（P<0.05、0.01）；模型组1和2大鼠均出现精神状况不佳，进食量降低，活动强度减弱等情况，且部分鼠出现腹泻，模型组2大鼠腹泻情况比模型组1更严重。对照组未出现大鼠死亡，阿霉素累积剂量为15 mg·kg^-1时，模型组1、2死亡率分别为30%、15.4%；累积剂量为20 mg·kg^-1时，模型组1、2死亡率分别为70%、46.2%；累积剂量为25 mg·kg^-1时，模型组2的死亡率为69.2%。与对照组比较，阿霉素累积给药15 mg·kg^-1时，模型组1左室舒张末期内径（LVIDd）、收缩期室间隔厚度（IVSs）、左室质量（LV Mass）均显著减小（P<0.05）；模型组2的舒张期室间隔厚度（IVSd）、IVSs、舒张期左室后壁厚度（LVPWd）、收缩期左室后壁厚度（LVPWs）、LV Mass均显著减小（P<0.05、0.01）。阿霉素累积给药20 mg·kg^-1时，模型组1的LVIDd、LVPWs、LV Mass均显著减小（P<0.05、0.01）；模型组2的左室射血分数（EF）、短轴缩短率（FS）、IVSd、IVSs、LVPWs均显著减小（P<0.01），左室收缩末期内径（LVIDs）、收缩期左室容积（LV Vols）显著增加（P<0.05）。阿霉素累积给药25 mg·kg^-1时，模型组2的FS、IVSd、IVSs、LV Mass均显著减小（P<0.01），LV Vols显著增加（P<0.05）。与对照组比较，模型组2的心脏指数显著增加（P<0.05）。与对照组比较，阿霉素累积给药15 mg·kg^-1时，模型组2的血清CK和CK-MB水平显著升高（P<0.01）；阿霉素累积给药20 mg·kg^-1时，模型组2的血清CK、LDH、CK-MB水平皆显著升高（P<0.01）。结论 阿霉素单次ip 5.0 mg·kg^-1，每2天1次，持续4次，累积剂量20 mg·kg^-1，造模效果更佳。

Objective To study the best administration scheme of adriamycin in the preparation of acute cardiotoxicity rat model. Methods Forty five male Wistar rats were numbered and randomly divided into control group (n = 12), model group 1 (n = 20) and model group 2 (n = 13). The rats in model group 1 were ip treated with 2.5 mg·kg^-1 adriamycin once every two days for 16 days, and the cumulative dose was 20 mg·kg^-1. The pharmacodynamic indexes were investigated when the cumulative dose was 15 and 20 mg·kg^-1. Model group 2 rats were ip treated with 5.0 mg·kg^-1 adriamycin once every two days for 10 days, and the cumulative dose was 25 mg·kg^-1. The pharmacodynamic indexes were investigated when the cumulative dose was 15, 20 and 25 mg·kg^-1. Rats in the control group were given the same dose of normal saline as model group 1, once every 2 d for 16 d. The general state, mortality, echocardiography, cardiac index and the levels of creatine kinase (CK), creatine kinase isoenzyme (CK-MB) and lactate dehydrogenase (LDH) in serum were observed. Results Compared with control group, the mass of rats in model group 1 decreased significantly on the 6th, 8th, 10th, 12th, 14th and 16th days(P < 0.05, 0.01), and the mass of rats in model group 2 decreased significantly on 4th, 6th, 8th and 10th days decreased significantly (P < 0.05, 0.01). The rats in model group 1 and 2 had poormental condition, decreased food intake and activity intensity, and some rats had diarrhea. The diarrhea in model group 2 was more serious than that in model group 1. When the cumulative dose of adriamycin was 15 mg·kg^-1, the mortality of model group 1 and 2 were 30% and 15.4% respectively; When the cumulative dose was 20 mg·kg^-1, the mortality of model group 1 and 2 were 70% and 46.2% respectively; When the cumulative dose was 25 mg·kg^-1, the mortality of model group 2 was 69.2%. Compared with control group, when the cumulative dose of adriamycin was 15 mg·kg^-1, the left ventricular end diastolic diameter (LVIDd), systolic ventricular septal thickness (IVSs) and left ventricular mass (LV mass) in model group 1 decreased significantly (P < 0.05); The diastolic ventricular septal thickness (IVSd), IVSs, diastolic left ventricular posterior wall thickness (LVPWd), systolic left ventricular posterior wall thickness (LVPWs) and LV mass in model group 2 decreased significantly (P < 0.05, 0.01). When the cumulative dose was 20 mg·kg^-1, the LVIDd, LVPWs and LV mass of model group 1 decreased significantly (P < 0.05, 0.01); In model group 2, left ventricular ejection fraction (EF), short axis shortening rate (FS), IVSd, IVSs, LVPWs decreased significantly (P < 0.01), left ventricular end systolic diameter (LVIDs) and systolic left ventricular volume (LV Vols) increased significantly (P < 0.05). When the cumulative dose was 25 mg·kg^-1, in model group 2, FS, IVS, D, IVS, s and LV mass decreased significantly (P < 0.01) and LV Vols increased significantly (P < 0.05). Compared with control group, the cardiac index of model group 2 increased significantly (P < 0.05). Compared with the control group, the levels of serum CK and CK-MB in model group 2 increased significantly when adriamycin was administered cumulatively at 15 mg·kg^-1 (P < 0.01). When doxorubicin was given 20 mg·kg^-1, the levels of serum CK, LDH and CK-MB in model group 2 increased significantly (P < 0.01). Conclusion Adriamycin 5.0 mg·kg^-1 was ip once every two days, totally four times, with cumulative dose of 20 mg/kg was the best effect was obtained.

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