阿霉素急性心脏毒性大鼠造模方法研究  

Study on model establishment of adriamycin induced acute cardiotoxicity in rats

作　　者：吕清波 潘均华 李帅[1] 王怡[1] 舒乐新[1] Lü Qingbo;PAN Junhua;LI Shuai;WANG Yi;SHU Lexin(Tianjin University of Traditional Chinese Medicine,Tianjin 301617,China)

机构地区：[1]天津中医药大学,天津301617

出　　处：《药物评价研究》2022年第2期301-307,共7页Drug Evaluation Research

摘　　要：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15mg·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<0Objective 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 poor mental 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

关 键 词：阿霉素 心脏毒性 心肌损伤 模型 

分 类 号：R926[医药卫生—药学]