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目的研究茵栀黄水提物(YZH)对α-异硫氰酸酯(ANIT)诱导的胆汁淤积小鼠的作用。方法小鼠按照体重随机分为6组:正常组、模型组、3个剂量(7.2,3.6,1.8 g·kg~(-1))YZH组及熊去氧胆酸(UDCA)组,均连续给药5d。给药后第6天,给与ANIT(75 mg·kg~(-1))制备胆汁淤积模型,然后继续给YZH或UDCA(120 mg·kg~(-1)),连续2 d。处死动物,取血、肝及肾组织,用HPLC-MS/MS测定血清胆酸含量,免疫印迹法考察胆酸转运体表达。结果 YZH可明显缓解肝损伤,并显著降低血清中胆酸、牛磺胆酸盐及甘氨胆酸盐含量,增加肝转运体Na+-牛磺胆酸共转运多肽(Ntcp)和多药耐药相关蛋白4(Mrp4)和肾机阴离子转运蛋白3(Oat3)的表达。结论 YZH对胆汁淤积小鼠有明显的改善作用,其机制可能与增加肝转运体Ntcp和Mrp4表达以及肾转运体Oat3的表达有关。
Objective To study the effect of Yin Zhi Huang water extract (YZH) on the cholestasis induced by α-isothiocyanate (ANIT) in mice. Methods The mice were randomly divided into 6 groups according to body weight: normal group, model group, 3 doses (7.2, 3.6, 1.8 g · kg -1) YZH group and ursodeoxycholic acid (UDCA) Administration 5d. On the 6th day after administration, the model of cholestasis was established with ANIT (75 mg · kg -1) and then continued to YZH or UDCA (120 mg · kg -1) for 2 days. The animals were sacrificed and blood, liver and kidney tissues were taken out. Serum cholic acid content was determined by HPLC-MS / MS. The expression of bile acid transporter was examined by immunoblotting. Results YZH could obviously relieve liver injury and significantly reduce the content of bile acid, taurocholate and glycocholate in serum, increase the expression of hepatic transporter Na + - taurocholic acid cotransported polypeptide (Ntcp) and multidrug resistance Related protein 4 (Mrp4) and renal anion transport protein 3 (Oat3) expression. Conclusion YZH can significantly improve the cholestasis in mice, and its mechanism may be related to the increase of hepatic transporter Ntcp and Mrp4 expression and the expression of renal transporter Oat3.