不同给药方案构建多柔比星致大鼠心肌损伤模型的效果比较  

Comparison of the effects of different administration regimens in constructing doxorubicin-induced myocardial injury models of rats

作　　者：焦浩淼 何张旭 JIAO Haomiao;HE Zhangxu(Department of Pharmacy,Zhengzhou Seventh People's Hospital,Zhengzhou 450016,Henan Province,China;Pharmacy College,Henan University of Chinese Medicine,Zhengzhou 450046,Henan Province,China)

机构地区：[1]郑州市第七人民医院药学部,河南郑州450016 [2]河南中医药大学药学院,河南郑州450046

出　　处：《新乡医学院学报》2025年第2期99-106,共8页Journal of Xinxiang Medical University

基　　金：中国博士后科学基金资助项目(编号:2022M721060)。

摘　　要：目的探讨3种多柔比星(DOX)给药方法所建立的心肌损伤大鼠模型心肌损伤的差异性,旨在为研究DOX致心肌损伤的保护剂提供更贴近临床的动物模型。方法将80只健康无特定病原级雄性Sprauge-Dawley(SD)大鼠随机分为对照组、模型A组、模型B组和模型C组,每组20只。对照组大鼠给予生理盐水2 mL尾静脉注射,每周1次,连续注射6周,停药观察1周;模型A组大鼠尾静脉注射DOX 0.8 mg·kg^(-1)·d-1,每周连续给药3 d,实验周期为6周,停药观察1周;模型B组大鼠尾静脉注射DOX 2.4 mg·kg^(-1),每周给药1次,实验周期为6周,停药观察1周;模型C组大鼠尾静脉注射DOX 7.2 mg·kg^(-1),每3周给药1次,实验周期为6周,停药观察1周。实验期间观察大鼠生命体征、精神状态,计算不同时间点的大鼠死亡率。DOX末次给药1周后,用小动物超声仪检测各组大鼠心功能,用仪器自带软件计算左心室射血分数(LVEF)和左心室短轴缩短率(LVFS)。停药1周后,使用酶标仪检测各组大鼠血清乳酸脱氢酶(LDH)活力及心肌特异性肌酸激酶(CK-MB)、超氧化物歧化酶(SOD)和丙二醛(MDA)水平。苏木精-伊红(HE)染色观察各组大鼠心肌组织病理学表现,Masson染色检测心肌组织纤维化程度,Western blot法检测各组大鼠心肌组织中α-SMA蛋白相对表达量。结果停药1周后,对照组大鼠身体状态无异常;与对照组比较,模型A组、模型B组、模型C组大鼠反应迟钝,进食差,活动减少;模型A组大鼠未出现脱毛和腹泻症状且尾部注射部位出现硬化,模型B组大鼠出现脱毛症状,模型C组大鼠出现脱毛和腹泻症状,且模型C组大鼠脱毛症状重于模型B组。对照组大鼠在7周的实验周期内未出现死亡,模型A组大鼠死亡率为15%(3/20),模型B组大鼠死亡率为10%(2/20),模型C组大鼠死亡率为35%(7/20)。模型A组、模型B组和模型C组大鼠的LVEF、LVFS值显著低于对照组,模型C组大鼠的LVEF、LVFS值显著低于模�Objective To explore the differences in constructing doxorubicin(DOX)-induced myocardial injury models of rats between three administration regimens and to provide a more accurate clinical animal model for the study of protectants against DOX-induced myocardial injury.Methods A total of 80 healthy male specific pathogen free(SPF)Sprauge-Dawley(SD)rats were randomly divided into the control group,the model A group,the model B group,and the model C group,with 20 rats in each group.The rats in the control group were injected with 2 mL of normal saline through the tail vein,once a week for 6 weeks,and the drug was discontinued for 1 week.The rats in the model A group were injected with DOX 0.8 mg·kg^(-1)·d-1 through the tail vein,continuous injection within 3 days every week for 6 weeks,and the drug was discontinued for 1 week.The rats in the model B group were injected with DOX 2.4 mg·kg^(-1) through the tail vein,once a week for 6 weeks,and the drug was discontinued for 1 week.The rats in the model C group were injected with DOX 7.2 mg·kg^(-1) through the tail vein,once every 3 weeks for 6 weeks,and the drug was discontinued for 1 week.Throughout the experiment,constant observation was maintained on the vital signs and mental state of the rats,while calculating their mortality rate at different time points.One week after the final administration of DOX,the cardiac function of rats in each group was assessed using a small animal sonograph,and the left ventricular ejection fraction(LVEF)and the left ventricular fraction shortening(LVFS)were computed with the software embedded in the instrument.One week after drug discontinuation,the level of lactate dehydrogenase(LDH),creatine kinase MB(CK-MB),superoxide dismutase(SOD),and malondialdehyde(MDA)was measured by a microplate reader.Hematoxylin and eosin(HE)staining was used to observe the histopathological manifestations of the myocardial myocardium,Masson staining was used to detect the degree of fibrosis in myocardial tissues,and Western blot(WB)was used to detect

关 键 词：多柔比星 心肌损伤 尾静脉注射 

分 类 号：R33[医药卫生—人体生理学]