环磷酰胺致S_(180)荷瘤小鼠肝损伤机制的实验研究

A study on mechanisms of liver injuries induced by cyclophosphamide in S_(180) mice

目的 观察环磷酰胺对S180荷瘤小鼠肝脏的损伤作用及探讨其发生机制。方法选S180荷瘤小鼠腹腔注射环磷酰胺60 mg·kg·d-1连续5天,停药后7天观察血清酶学指标、肝组织中氧化及抗氧化指标的变化以及肝组织病理学改变。结果 血清谷丙转氨酶(ALT)无显著变化,肝组织中的丙二醛(MDA)显著升高,还原型谷胱甘肽(GSH)、超氧化物歧化酶(SOD)、过氧化氢酶(CAT)、谷胱甘肽S-转移酶(GST)、谷胱甘肽过氧化物酶(GSH-PX)显著降低。病理学检查发现环磷酰胺引起肝细胞点状及小灶性坏死,坏死区及汇管区炎性细胞浸润。结论 环磷酰胺造成的S180小鼠肝细胞损伤机制与化疗引起的氧化应激有关。

Objective To investigate the mechanisms of liver injuries induced by cyclophosphamide (CTX) in S180 mice. Methods The pathologic examination on liver tissue, serum transaminases (ALT), oxidative parameters (MDA) and anti-oxidative parameters (GSH, SOD, CAT, GST, GSH-PX) of the liver tissue were observed on the 7th day after administration of CTX (60 mg·kg-1·d-1×5d ip). Results Serum ALT were not changed significantly. MDA in liver tissue increased and GSH, SOD, CAT, GST, GSH-PX declined. Pathologic examination showed that spotty and focal necroses of the liver were found and there were infiltrations of inflammatory cells in the necrotic and portal areas. Conclusion CTX could induce liver injuries of mice after cyclophosphamide. The mechanisms of the injuries were contributed to the oxidative stress induced by CTX.