黛矾散对原发性胆汁性胆管炎小鼠肝细胞膜多重药物抗性相关蛋白2的影响

Effects of Daifansan on liver cell membrane transporter MRP2 with primary biliary cirrhosis animal models

目的:观察黛矾散及其各组分对用聚肌胞苷酸(PolyⅠ:C)建立的原发性胆汁性胆管炎(PBC)小鼠多重药物抗性相关蛋白2(MRP2)的影响,以进一步探究黛矾散治疗PBC的机理。方法:将60只雌性C57BL/6小鼠随机分成正常组、模型组、青黛组、明矾组、黛矾散组、熊去氧胆酸(UDCA)组,应用PolyⅠ:C建立PBC模型,观察黛矾散及其组分对PBC小鼠血清生化指标、肝组织学及肝细胞膜转运体MRP2的影响。结果:与正常组比较,模型组小鼠AMA、ALP显著升高(P<0.05),MRP2 mRNA及蛋白表达水平显著降低(P<0.05);与模型组比较,各治疗组小鼠AMA、ALP显著降低(P<0.05),MRP2 mRNA及蛋白表达水平分别有不同程度的升高,其中黛矾散组及熊去氧胆酸组升高最为显著(P<0.05)。病理结果显示正常组小鼠肝细胞排列整齐,无炎症细胞浸润及胆管增生;模型组小鼠肝小叶结构存在,肝细胞普遍中-重度变性,门管区炎症细胞浸润及纤维组织轻度增生,向周围肝组织穿插,呈早期肝硬化趋势;治疗组小鼠肝脏炎症细胞浸润及胆管增生有不同程度减轻。结论:黛矾散及其组分能不同程度改善PBC模型小鼠的肝组织病理变化、提高MRP2基因的转录和蛋白表达水平。

Objective:To observe the effect of Daifansan and its components on primary biliary cirrhosis(PBC) animal model which induced by polyinosinic acid(Poly I:C),to further explore the mechanism of daifansan treatment of primary biliary cirrhosis.Methods:Sixty female C57 BL-6 mice were randomly divided into normal group,model group,Qingdai group,alum group,Daifansan group,ursodeoxycholic acid(UDCA) group,using Poly 1:C to establish PBC animal model to observe effects of Daifansan and its components onserum biochemical indexes,pathological changes of the liver and liver cell membrane transporters MRP2.Results:compared with the normal group,AMA,ALP in model group significantly increased(P<0.05),the level of mRNA and MRP2 protein significantly decreased(P<0.05);compared with the model group,AMA,ALP in treatment group decreased significantly(P<0.05),the level of mRNA and MRP2 protein increased in different degrees,among them,Daifansan group and ursodeoxycholic acid group increased significantly(P<0.05).The pathological results showed that hepatic cells of normal group arranged neatly,no inflammatory cell infiltration and hyperplasia of bile duct;hepatic lobules structure existed in model group,hepatocytes were commonlyin moderate to severe degeneration,inflammatory cell infiltratedin portal area,fibrous tissue hyperplasia slightly and inserted into surrounding livertissue,showing the tendency of early liver cirrhosis;in treatment group,inflammatory cell infiltration and hyperplasia of bile duct were alleviated.Conclusion:Daifansan and its components can promote MRP2 gene transcription and protein expression of PBC mice model established by Poly I:C.