甘草酸单铵对异烟肼致大鼠肝损伤的保护作用及其机制

目的:考察甘草酸单铵(MAG)对异烟肼(INH)诱导的大鼠肝损伤的保护作用及其对肝脏转运体Na⁺-牛磺胆酸共转运多肽(Na⁺-taurocholate cotransporting polypeptide,NTCP)及多药耐药相关蛋白2(multidrug resistance protein 2,Mrp2)的调节作用。方法:Wistar雄性大鼠45只,随机分为9组,即对照组,异烟肼肝损伤组(INH组),甘草酸单铵治疗组(MAG组),以上每组又各分为干预7,14,21 d组。INH组大鼠灌胃INH 60 mg·kg^-1·d^-1;MAG组大鼠灌胃MAG 45 mg·kg^-1·d^-1 3 h后灌胃INH。干预结束后,处死大鼠,通过血清生化指标、肝脏病理及Ntcp、Mrp2蛋白表达对各组大鼠进行评价对比。结果:血清生化指标与肝脏病理结果显示,INH诱导的大鼠肝损伤具有时间依赖性,而MAG对INH诱导的大鼠肝损伤具有保护作用,且存在时间依赖性;与INH组相比,MAG干预21 d对肝脏转运体Ntcp及Mrp2表达具有明显下调作用(P<0.05)。结论:MAG对INH诱导的肝损伤的保护作用可能与下调肝细胞膜转运体Ntcp与Mrp2的表达有关。

Protective effects and mechanism of ammonium glycyrrhizinate on isoniazid induced liver injuries in rats

OBJECTIVE To preliminarily study on effects of ammonium glycyrrhizinate on isoniazid (INH) induced liver injuries in rats,and expression of Na⁺-taurocholate cotransporting polypeptide (Ntcp) and multidrug resistance protein 2 (Mrp2).METHODS Rats were randomly divided into nine groups,namely normal group,INH group and ammonium glycyrrhizinate (MAG) group,each group was further divided into 7,14,21 d groups,respectively.Rats in INH group were orally administered INH (60 mg·kg^-1·d^-1).Rats in MAG group were orally administered MAG (45 mg·kg^-1·d^-1) 3 h before INH administration.When treatment was finished,rats were evaluated by comparing biochemical indicators of blood serum,hepatic pathology and expression of Ntcp and Mrp2.RESULTS Serum biochemical indicators and hepatic pathology showed that INH could induce liver injuries in a time-dependent manner.A protective effect was observed after MAG treatment,also in a time-dependent manner.Compared to INH group,MAG could significantly decrease expression of Ntcp and Mrp2 at 21 d.CONCLUSION MAG can relieve INH induced liver injuries of rats,and may be related to down regulation of Ntcp and Mrp2 in liver.