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目的:本文基于肝细胞膜转运体多药耐药相关蛋白2(multidrug resistance protein 2,Mrp2)和Na+-牛磺酸钠共转运体(sodium taurocholate cotransporting polypeptide,Ntcp),初步探究甘草酸单铵(monoammonium glycyrrhizinate,MAG)对利福平(rifampicin,RIF)致大鼠肝损伤的保护作用及机制。方法:Wistar雄性大鼠随机分为3组:对照组(control组):灌胃等容量的生理盐水;RIF肝损伤组(RIF组):灌胃RIF60 mg·kg-1·d-1;MAG治疗组(MAG+RIF组):灌胃MAG45 mg·kg-1·d-13 h后灌胃RIF60 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:与对照组相比,RIF组给药7,14,21 d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(P<0.01);MAG+RIF组血清生化指标与对照组之间无显著差异,与RIF组相比其HAI评分显著降低(P<0.05)。给药7,14,21 d时,RIF组较对照组Mrp2的表达均显著升高(P<0.05),而MAG+RIF组Mrp2的表达均显著低于RIF组(P<0.05)。给药期间,各组Ntcp的表达均无显著差异(P>0.05)。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。
OBJECTIVE: To investigate the effects of monoammonium (glycyrrhizinate) on the expression of multidrug resistance protein 2 (Mrp2) and sodium taurocholate cotransporting polypeptide (Ntcp) glycyrrhizinate (MAG) on rat liver injury induced by rifampicin (RIF) and its mechanism. Methods: Wistar male rats were randomly divided into 3 groups: control group (control group): normal saline with intragastric administration; RIF group with liver injury (RIF group): RIF60 mg · kg -1 · d -1; Treatment group (MAG + RIF group): RIF60 mg · kg-1 · d-1 was intragastrically administrated after intragastric administration of MAG45 mg · kg-1 · d-13 h. On the 7th, 14th and 21st day after administration, 5 rats in each group were randomly selected to determine the biochemical indexes, and the liver tissues were taken for pathological examination. The liver histopathological changes were observed and the liver histology activity index (HAI) Western blotting was used to detect the expression of Mrp2 and Ntcp in liver tissue. Results: Compared with the control group, some serum biochemical parameters of RIF group increased significantly and the pathological HAI score increased significantly (P <0.01) at 7, 14 and 21 d after administration. In the MAG + RIF group, serum biochemistry There was no significant difference between the index and the control group, and the HAI score was significantly lower than that of the RIF group (P <0.05). At 7, 14 and 21 d, the expression of Mrp2 in RIF group was significantly higher than that in control group (P <0.05), while the expression of Mrp2 in MAG + RIF group was significantly lower than that in RIF group (P <0.05). During administration, there was no significant difference in Ntcp expression between groups (P> 0.05). Conclusion: The mechanism of rifampicin-induced liver injury may be related to upregulation of Mrp2. MAG can protect rifampin-induced liver injury, and its hepatoprotective effect may be related to its down-regulation of Mrp2.