目的 研究應(yīng)用阿霉素制備急性心臟毒性大鼠模型的最佳給藥方案。方法 雄性Wistar大鼠45只，分別編號并隨機(jī)分為對照組（n=12）、模型組1（n=20）和模型組2（n=13）。模型組1大鼠按2.5 mg·kg^-1 ip阿霉素，每2天1次，持續(xù)16 d，累積劑量為20 mg·kg^-1，考察累積劑量為15、20 mg·kg^-1時的藥效學(xué)指標(biāo)；模型組2大鼠按5.0 mg·kg^-1 ip阿霉素，每2天1次，持續(xù)10 d，累積劑量為25 mg·kg^-1，考察累積劑量為15、20、25 mg·kg^-1時藥效學(xué)指標(biāo)；對照組大鼠給予與模型組1同等劑量的生理鹽水，每2天1次，持續(xù)16 d。觀察各組大鼠的一般狀態(tài)、死亡率、超聲心動圖、心臟指數(shù)以及血清中肌酸激酶（CK）、肌酸激酶同工酶（CK-MB）、乳酸脫氫酶（LDH）水平。結(jié)果 與對照組比較，模型組1大鼠第6、8、10、12、14、16天體質(zhì)量顯著下降（P<0.05、0.01）；模型組2第4、6、8、10天體質(zhì)量顯著下降（P<0.05、0.01）；模型組1和2大鼠均出現(xiàn)精神狀況不佳，進(jìn)食量降低，活動強(qiáng)度減弱等情況，且部分鼠出現(xiàn)腹瀉，模型組2大鼠腹瀉情況比模型組1更嚴(yán)重。對照組未出現(xiàn)大鼠死亡，阿霉素累積劑量為15 mg·kg^-1時，模型組1、2死亡率分別為30%、15.4%；累積劑量為20 mg·kg^-1時，模型組1、2死亡率分別為70%、46.2%；累積劑量為25 mg·kg^-1時，模型組2的死亡率為69.2%。與對照組比較，阿霉素累積給藥15 mg·kg^-1時，模型組1左室舒張末期內(nèi)徑（LVIDd）、收縮期室間隔厚度（IVSs）、左室質(zhì)量（LV Mass）均顯著減小（P<0.05）；模型組2的舒張期室間隔厚度（IVSd）、IVSs、舒張期左室后壁厚度（LVPWd）、收縮期左室后壁厚度（LVPWs）、LV Mass均顯著減?。?i>P<0.05、0.01）。阿霉素累積給藥20 mg·kg^-1時，模型組1的LVIDd、LVPWs、LV Mass均顯著減小（P<0.05、0.01）；模型組2的左室射血分?jǐn)?shù)（EF）、短軸縮短率（FS）、IVSd、IVSs、LVPWs均顯著減?。?i>P<0.01），左室收縮末期內(nèi)徑（LVIDs）、收縮期左室容積（LV Vols）顯著增加（P<0.05）。阿霉素累積給藥25 mg·kg^-1時，模型組2的FS、IVSd、IVSs、LV Mass均顯著減小（P<0.01），LV Vols顯著增加（P<0.05）。與對照組比較，模型組2的心臟指數(shù)顯著增加（P<0.05）。與對照組比較，阿霉素累積給藥15 mg·kg^-1時，模型組2的血清CK和CK-MB水平顯著升高（P<0.01）；阿霉素累積給藥20 mg·kg^-1時，模型組2的血清CK、LDH、CK-MB水平皆顯著升高（P<0.01）。結(jié)論 阿霉素單次ip 5.0 mg·kg^-1，每2天1次，持續(xù)4次，累積劑量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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