论文部分内容阅读
目的观察利福平(RFP)引起的小鼠肝内胆汁淤积及其动态过程,为进一步探讨胆汁淤积性肝损伤的机制奠定基础。方法本实验设置3个模型组,模型1:小鼠分别经灌胃给予RFP(100、150、200mg/kg),连续1周,末次给药后6h取材;模型2:小鼠分别经灌胃给予RFP200mg/(kg.d),连续1或2周,末次给药后6h取材;模型3:分别灌胃给予小鼠RFP200mg/kg后于不同时点0.5、2、6、12h取材。所有小鼠均收集血液和肝组织,检测血清丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、碱性磷酸酶(ALP)、总胆红素(TB)和结合胆红素(DB);检测血清和肝组织胆汁酸(TBA)水平;观察小鼠肝脏病理改变。结果给予RFP200mg/(kg.d)1周后,小鼠血清TB上升近70倍,DB上升约82倍,ALP上升约1.5倍,TBA上升约4倍并伴有血清ALT和AST轻度升高;肝脏组织TBA上升约2.5倍;肝脏组织HE染色显示肝细胞出现脂肪变性、轻度坏死和炎症。单次给予RFP200mg/kg30min后血清TB、DB、ALP和TBA即开始显著上升,给药后2～6h达到高峰,12h呈下降趋势;ALT和AST的变化趋势与之一致;单次给予RFP不同时点后均未观察到小鼠肝脏组织病理发生改变。结论单次或连续1周给予RFP200mg/kg均引起小鼠肝内胆汁淤积,并伴有轻度的肝细胞损伤。
Objective To observe the intrahepatic cholestasis induced by rifampicin (RFP) in mice and its dynamic process, and lay a foundation for further study on the mechanism of cholestatic liver injury. METHODS: Three models were set up in this study. Model 1: mice were given RFP (100,150, 200 mg / kg) by gavage for 1 week and 6 hours after the last administration. Model 2: Given RFP200mg / (kg.d), continuous 1 or 2 weeks, 6h after the last dose; Model 3: mice were given intragastric administration of RFP200mg / kg at different time points 0.5,2,6,12 h drawn. Blood and liver tissues were collected from all the mice. Serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total bilirubin (TB) Bilirubin (DB); serum and liver tissue were measured bile acid (TBA) levels; pathological changes observed in mice liver. Results One week after the RFP was given at 200 mg / (kg · d), the serum TB increased nearly 70-fold, DB increased about 82-fold, ALP increased about 1.5-fold, TBA increased about 4-fold and accompanied with mild increase of serum ALT and AST ; Liver tissue TBA increased by about 2.5 times; liver tissue HE staining showed fatty degeneration of liver cells, mild necrosis and inflammation. Serum TB, DB, ALP and TBA began to increase significantly after given 200 mg / kg of RFP for 30 min, reached the peak at 2 ~ 6 h after administration, and decreased at 12 h. The change trend of ALT and AST was consistent with that of single dose of RFP No pathological changes of liver tissues were observed in mice. Conclusions Single or continuous 1-week RFP administration at 200 mg / kg caused intrahepatic cholestasis in mice with mild hepatocellular injury.