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目的建立胆道结扎的大鼠模型,观察川西獐牙菜活性单体齐墩果酸(oleanolic acid,OA)对胆道结扎所致的肝外胆汁淤积的保护作用,及其对多药耐药相关蛋白3(multidrug resistanceassociated protein 3,Mrp3)、核受体Lrh-1的调控作用。方法采用随机数字表法将15只SD大鼠分为3组:假结扎组(Sham组)、胆道结扎组(BDL组)、齐墩果酸组(BDL+OA组),每组5只。分别用生理盐水、齐墩果酸处理7 d后,收集组织标本,HE染色检测肝脏损伤程度,Western blot及RT-PCR检测Mrp3和Lrh-1在蛋白及mRNA水平的变化。结果 HE染色结果显示BDL+OA组肝脏损伤程度较胆道结扎组明显减轻;Western blot结果表明BDL+OA组Mrp3表达较Sham组增加2.4倍,Lrh-1表达增加1.8倍;RT-PCR结果显示BDL+OA组Mrp3表达较Sham组增加3.2倍,Lrh-1表达升高2.2倍。结论川西獐牙菜单体齐墩果酸对胆道结扎所致大鼠胆汁淤积性肝损伤具有保护作用,而这种保护作用可能与Lrh-1、Mrp3有关。
Objective To establish a rat model of biliary ligation and observe the protective effect of Oleanolic Acid (OA), an active monomer of Swertia sinensis, on extrahepatic cholestasis caused by biliary ligation and its effect on multidrug resistance-related protein 3 (multidrug resistanceassociated protein 3, Mrp3), nuclear receptor Lrh-1 regulation. Methods Fifteen SD rats were randomly divided into three groups: Sham group, BDL group, and oleanolic acid group (BDL + OA group), with 5 rats in each group. After treated with saline and oleanolic acid for 7 days, the tissue samples were harvested, the degree of hepatic injury was detected by HE staining, and the changes of Mrp3 and Lrh-1 protein and mRNA were detected by Western blot and RT-PCR. Results The results of HE staining showed that the degree of hepatic injury in BDL + OA group was significantly lower than that in the biliary ligation group. The Western blot results showed that Mrp3 expression in BDL + OA group was 2.4-fold and Lrh-1 increased 1.8-fold compared with Sham group. RT- + OA group Mrp3 expression increased 3.2-fold compared with Sham group, Lrh-1 expression increased 2.2-fold. Conclusion Oleanolic acid, a monomer of Swertia chinensis, has a protective effect on cholestatic liver injury induced by biliary ligation in rats, and this protective effect may be related to Lrh-1 and Mrp3.