Aim Toexamineliverdamagebyrifampi-cin and hepatic gene expression related to bile acid me-tabolisminmice.Methods Adultmalemicewere given rifampicin(180 mg·kg-1 ,po)daily for 30 days and(90 mg·kg-1 ,po)daily for 90 days,blood bio-chemistry,histopathology,and gene expression were examined.Results Rifampicinincreasedanimalliver index and serum enzyme activities. Histopathology showed steatosis and spotted feathery-like degenera-tion.Rifampicin increased the expression of CYP7A1 after 30 and 90 days of administration,along with in-creased FXR and SHP.Rifampicin reduced the expres-sion of BSEP after 30 days of high dose administration. Conclusion Repeatedadministrationofrifampicin may cause liver injury and intrahepatic cholestasis in mice,and these effects are associated with the altera-tion of gene expression related to bile acid metabolism.%目的观察利福平长期给药引起小鼠的肝损伤及其对胆汁酸代谢通路相关基因的影响。方法1d1次灌胃给予♂昆明种小鼠180 mg·kg－1利福平连续30 d 与90 mg· kg－1利福平连续90 d；麻醉取血、肝脏，称肝重，检测血清谷丙转氨酶（ALT），观察肝脏组织的病理变化；提取肝脏总RNA并采用RT-PCR法检测胆汁酸代谢相关基因mRNA的表达情况，提取肝脏总蛋白并采用Western blot 法检测相关蛋白的表达。结果连续给予利福平180 mg·kg－130 d和90 mg·kg－190 d，小鼠肝重系数增加，肝脏发生明显病理改变，表现为肝细胞水肿、羽毛样变性与脂肪变性，且利福平180 mg·kg－130 d病理改变较严重；连续给药180 mg·kg－1利福平30 d 可使胆酸代谢基因胆固醇7α-羟化酶（CYP7A1）、法尼醇受体（FXR）、小分子异源二聚体伴侣（SHP）表达增加，胆盐输出泵（BSEP）的表达降低；连续给药90 mg·kg－1利福平90 d，仅可发现胆酸代谢基因胆固醇7α-羟化酶（CYP7A1）表达增加。结论利福平对小鼠具有明显肝毒性，引起胆汁淤积性肝损伤；其影响CYP7A1与BSEP的基因表达可能是其导致胆汁淤积性肝损伤的机制之一。
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