6种常用抗肿瘤药物致小鼠肝损害程度的比较研究  

Comparison of Liver Injury Degree in Mice Induced by 6 Kinds of Common Antineoplastic Drugs

作　　者：叶冬梅[1] 陈晓宇[1] 兰顺[1] 李重勤[2] 

机构地区：[1]广西壮族自治区人民医院,南宁市530021 [2]桂林医学院药学系,桂林市541004

出　　处：《中国药房》2011年第29期2720-2722,共3页China Pharmacy

基　　金：广西壮族自治区卫生厅计划课题(Z2009170)

摘　　要：目的:比较6种常用抗肿瘤药物的致肝损害程度。方法:取小鼠随机分为7组,每组10只,分别尾静脉注射生理盐水及临床常用剂量的顺铂(17mg·kg-1)、卡铂(67mg·kg-1)、紫杉醇(30mg·kg-1)、多西紫杉醇(17mg·kg-1)、吉西他滨(222mg·kg-1)、长春瑞滨(5.6mg·kg-1),给药第3天检测各组小鼠肝功能生化、肝组织氧化和抗氧化指标,光电镜观察肝组织病理学变化。结果:与生理盐水组比较,6个药物组给药第3天均出现肝功能生化指标与病理组织形状改变:天门冬氨酸氨基转移酶(AST)、碱性磷酸酶(ALP)、丙二醛(MDA)活性均明显升高,还原型谷胱甘肽(GSH)活性均明显降低(P<0.05或P<0.01);镜下显示细胞脂肪变性最严重的是多西紫杉醇,肝细胞坏死和瘀胆最严重的是多西紫杉醇和吉西他滨;综合各指标显示,6种药物均可致肝损害,严重程度排序为:吉西他滨≈多西紫杉醇>长春瑞滨>顺铂≈紫杉醇>卡铂。结论:6种常用抗肿瘤药物在给药第3天均出现不同程度的致肝损害,其中以吉西他滨和多西紫杉醇致肝损害较严重,建议临床使用时及早预防性应用抗氧化剂。OBJECTIVE： To compare the degree of liver injury induced by 6 kinds of common antineoplastic drugs. METH- ODS： 70 mice were randomly divided into 7 groups with 10 mice in each group. They were given normal saline and common dose of cisplatin （17 mg.kg-1）, carboplatin （67 mg.kg-1）, paclitaxel （30 mg.kg-1）, docetaxel （17 mg.kg-1）, gemcitabine （222 mg. kg-1）, vinorelbine （5.6 mg.kg-1）, respectively. At the 3rd day, the parameters of hepatic biochemistry, liver oxidation and antioxidation and histopathologic change in hepatic tissue were observed. RESULTS： Compared with normal saline group, the parameter change of serum biochemistry and pathological change were observed in 6 trial groups at the 3rd day： the activities of AST, ALP and MDA increased significantly while GSH activity decreased significantly （P〈0.05 or P〈0.01） ; the most serious fatty change was caused by docetaxel, and docetaxel and gemcitabine caused the most serious liver cell necrosis and cholestasia. These parameters all indicated that 6 kinds of drugs could cause liver injury, the degree of liver injury in descendent order were gemcitabine≈ docetaxel〉vinorelbine〉cisplatin≈paclitaxel〉carboplatin. CONCLUSION： 6 kinds of common antineoplastic drugs can cause different degrees of liver injury at the 3rd day after administration, especially gemcitabine and docetaxel. It is suggested to apply antioxidant as soon as possible in the clinic.

关 键 词：顺铂 卡铂 紫杉醇 多西紫杉醇 吉西他滨 长春瑞滨 小鼠 肝损害 

分 类 号：R969[医药卫生—药理学] R979.1[医药卫生—药学]