不同给药次数环磷酰胺诱导小鼠肝损伤的对比研究.docVIP

不同给药次数环磷酰胺诱导小鼠肝损伤的对比研究 　　作者：张善玉,朴娟玉,宛莹,刘佳　　作者单位：延边大学药学院，吉林 延吉 　　【摘要】 [目的]比较不同给药次数环磷酰胺所诱导的小鼠肝损伤程度.[方法]分别隔日腹腔注射给予不同组别小鼠80mg/kg环磷酰胺，给药次数分别为1,2,3,5次，观察停药后各组小鼠血清生物化学指标、肝组织内氧化及抗氧化指标及肝组织病理学改变.[结果]给药1次及5次组小鼠血清转氨酶显著增高;给药3次组小鼠肝组织内还原型谷胱甘肽及谷胱甘肽过氧化物酶活性明显降低;给药5次组小鼠肝组织内丙二醛含量明显升高，还原型谷胱肽、超氧化物歧化酶及谷胱甘肽过氧化物酶活性明显降低.[结论]随着环磷酰胺给药次数的增多,小鼠肝组织中氧化及抗氧化指标及病理学改变更为明显，但血清生物化学指标的变化与给药次数无显著相关. 　　【关键词】 环磷酰胺;肝;创伤和损伤;小鼠 　　Comparative study of the liver injury induced with different medication times of cyclophosphamide in mice 　　ZHANG Shanyu, PIAO Juanyu, WAN Ying, LIU Jia 　　(Yanbian University College of Pharmacy, Yanji 133000， Jilin， China) 　　ABSTRACT:OBJECTIVETo compare the degrees of the liver injury induced with different medication times of cyclophosphamide (CP) in mice.METHODSMice in different groups were subjected to intraperitoneal injection of CP(80mg/(kgod)), for every other day with 1, 2, 3 and 5 times, and the serum biochemistry parameters, oxidation and antioxidation parameters, and histopathologic changes in hepatic tissue after discontinuation were observed.RESULTSThe serum transaminase increased significantly in the 1 time and 5 times groups, the activities of reduced glutathione and glutathione peroxidase decreased obviously in the 3 times group, and the content of malonaldehyde increased in liver tissue and the activities of reduced glutathione, superoxide dismutase and glutathione peroxidase decreased significantly in the 5 times group.CONCLUSIONThe changes of oxidation and antioxidation parameters and pathology lesion in liver tissue are more serious along with increasing of number of times of administrating CP, but changes of serum biochemistry parameters are not significantly correlated with number of times of administrating CP. 　　Key words:cyclophosphamide;liver;wounds and injuries;mice 　　目前，化学治疗是肿瘤治疗的主要手段，但化学治疗药物在杀伤肿瘤细胞的同时，亦可对机体正常组织产生不同程度损伤,近年来化学治疗引起的肝损伤备受关注.已有研究结果表明，环磷酰胺可致肝损伤[14]，并已见利用环磷酰胺制作实验性肝细胞损伤模型的报道[5].在一些中草药拮抗环磷酰胺毒副作用的研究中发现,不同剂量及次数的环磷酰胺