氧化应激在利福平所致大鼠肝损伤适应性模型中的作用

目的 探讨利福平致大鼠肝损伤适应性现象及氧化应激可能涉及的参与过程。方法 将正常对照组和利福平实验组大鼠各16只分别予以生理盐水10 mL/（kg·d）和利福平混悬液100 mg/（kg·d）每日一次空腹灌胃，共持续7周，动态监测大鼠灌胃当天、第14天、第28天和第49天血清转氨酶、胆红素和碱性磷酸酶水平。于第14天处死两组各4只大鼠，第49天处死剩余大鼠，检测肝脏超氧化物歧化酶（SOD）、丙二醛（MDA）、谷胱甘肽-过氧化物酶（GSH-PX）活性，并观察其肝组织病理学改变。结果 与正常组相比，利福平实验组大鼠血清谷丙转氨酶（ALT）、谷草转氨酶（AST）、总胆红素（TB）、直接胆红素（DB）水平在第14天达高峰，之后呈缓慢下降趋势（P<0.05），至第49天时，与正常组相比差异无统计学意义（P>0.05）。相较正常组，利福平实验组大鼠MDA水平偏高，而SOD与GPX活性偏低（P<0.05）。大体标本可见利福平实验组大鼠肝脏黄染，光镜下可见肝组织存在脂肪变性、轻度坏死和炎症。结论 利福平可导致大鼠肝损伤适应性现象，且氧化应激在一定程度上参与了上述过程。

Role of oxidative stress in adaptive models of hepatic injury induced by rifampicin in rats

Objective To discuss the adaption phenomenon to hepatic injury induced by rifampicin in rats and the possible role or process oxidative stress might be involved in.Methods The laboratory rats in the control group and the rifampicin group (each n=16) were fed by lavage once daily with 0.9% normal saline 10 mL/(kg·d) or rifampicin suspension 100 mg/(kg·d), respectively.During the course of 7-week successive drug lavage, the serum levels of transaminase, bilirubin and ALP of rats were dynamically monitored at the first, 14th, 28th, 49th day.When 4 rats in each group were killed at the 14th day, and the rest rats being killed at the 49th day, their hepatic histopathological changes were observed and their hepatic levels of SOD, MDA and GSH-PX were measured, respectively.Results Compared with the control group, the serum levels of ALT, AST, TB and DB of rats in the rifampicin group reached its peak at the 14th day, followed by a trend of slow decline (P<0.05), and at the 49th day there was no significant difference between the two groups (P>0.05).The rifampicin group showed much higher level of hepatic MDA and much lower levels of hepatic SOD and GPX in comparison with the control group (P<0.05).The gross liver samples of rats in the rifampicin group were found to be stained yellow, and further under microscopy, the hepatic steatosis, mild necrosis and inflammation were observed.Conclusion Administration of rifampicin could lead to the adaption phenomenon to hepatic injury in rats, and oxidative stress might be involved in such process.