甘草酸单铵保护利福平致大鼠肝损伤的机制初探周利婷1宋燕青1.DOC

甘草酸单铵保护利福平致大鼠肝损伤的机制初探 周利婷 1 （） [摘要] 目的Na+-牛磺酸钠共转运体（sodium taurocholate cotransporting polypeptide, Ntcp）甘草酸单铵（onoammonium glycyrrhizinate，MAG）利福平（ifampicin，RIF）方法Wistar雄性大鼠随机分为3组：正常组（control组）：灌胃等容量的生理盐水；RIF肝损伤组（RIF组）：灌胃RIF 60 mg·kg-1·d-1；MAG治疗组（MAG + RIF组）：灌胃MAG 45 mg·kg-1·d-1 3 h后灌胃RIF 60 mg·kg-1·d-1。给药第7、14、21天时，各组分别随机取5只大鼠分离血清测定生化指标；取肝组织做病理切片，观察肝脏组织病理学变化并进行“肝组织学活动指数（HAI）”评分；采用 Western blotting法检测肝组织Mrp2和Ntcp蛋白表达量。结果：与正常组相比，RIF组给药7、14、21天时，其部分血清生化指标呈明显上升趋势，肝脏病理学HAI分值显著增加（P0.01）；MAG + RIF组RIF组相比其HAI评分显著降低（P0.05）。给药7、14、21天时，RIF组较正常组Mrp2的表达均显著升高（P0.05），而MAG + RIF组Mrp2RIF组（P0.05）。给药期间，各组Ntcp的表达均无显著差异（P0.05）。结论：利福平肝损伤机制可能与其上调Mrp2有关，MAG可保护利福平诱导的肝损伤，且其保肝作用可能与其下调Mrp2有关。 [关键词]Na+-牛磺酸钠共转运体 onoammonium Glycyrrhizinate on Hepatic Injury Induced by Rifampicin in Rats ZHOU Li-ting1, SONG Yan-qing 1, QU Xiao-yu1, ZHANG Si-xi1, WU Xin-an 2,＊ (1. Department of Pharmacy, Jinlin University First Hospital, Changchun 130000,China; 2. Department of Pharmacy, 1st Hospital of Lanzhou University, Lanzhou 730000, China) [ABSTRACT]: OBJECTIVE Based on the hepatobiliary membrane transporters to investigate the mechanisms of rifampicin (RIF) induced liver injury and monoammonium glycyrrhizinate (MAG) on RIF induced hepatotoxicity and the underlying mechanisms in rats. METHODS Male Wistar rats were randomly divided into three groups: control, RIF and MAG group. Rats in RIF group were orally administered with RIF (60 mg·kg-1·d-1), rats in control group were orally administered with saline; while rats in MAG group were orally administrated with MAG (45 mg·kg-1·d-1) 3 h before RIF (60 mg·kg-1·d-1). Drugs were given to rats once a day for successive 21 days. At 7, 14, and 21 days after drugs administration, 5 rats in each group were randomly selected and fasted for 6 h. Blood were collected by abdominal aortic puncture, and the serum was obtained for ALT, AST, TBIL, DBIL, IBIL and TBA analysis. Liver were removed, one part for histological analysis; the other part for Western blotting analysis t