鞣料云实酸治疗胆汁淤积的分子机制研究  

The molecular mechanism of Tannin cloudy acid on treating cholestasis

作　　者：李尤玲 李刚 许杰 LI You-ling;LI Gang;XU Jie(Integrated TCM&Western Medicine Department,People's Hospital Affiliated to Hubei Medical College,Shiyan 442000,Hubei,China)

机构地区：[1]湖北医药学院附属人民医院中西医结合科,湖北十堰442000 [2]湖北医药学院附属人民医院全科医学科,湖北十堰442000 [3]湖北中医药大学中医临床学院,湖北武汉430060

出　　处：《广东医学》2019年第21期2991-2999,共9页Guangdong Medical Journal

基　　金：湖北省教育厅科学技术研究项目计划(编号:D20172103)

摘　　要：目的探讨鞣料云实酸在体外通过法尼酯衍生物X受体(FXR)相关通路对肝内胆汁淤积的改善作用。方法用不同浓度(25、50、100μg/mL)的鞣料云实酸处理LO2细胞。在细胞实验中,FXR表达由慢病毒转导或GW4064处理上调,由siRNA技术或guggulsterones治疗下调。采用实时PCR和Western blot检测FXR、SHP1、SHP2、CYP7A1、NTCP的mRNA和蛋白水平。结果鞣料云实酸增加了FXR、SHP1、SHP2的mRNA和蛋白表达水平,并降低了CYP7A1、NTCP的mRNA和蛋白表达水平。在使用不同的方法对FXR进行上调或下调后,鞣料云实酸仍然可以增加FXR、SHP1、SHP2的mRNA和蛋白表达水平,同时降低CYP7A1和NTCP的蛋白表达水平,特别是在高浓度的时候。结论鞣料云实酸在肝细胞中发挥保护作用,可以通过刺激FXR相关的通路阻止肝内胆汁淤积的有害活动。Objective To investigate the effects of Tannin cloudy acid on alleviating intrahepatic cholestasis by regulating liver FXR(farnesoid X receptor)-associated pathways in vitro.Methods Cells were treated with different concentrations of Tannin cloudy acid.FXR expression was up-regulated by either lentiviral transduction or GW4064 treatment,and down-regulated by either siRNA technology or treatment with guggulsterones.Real-time PCR and Western blot were employed to detect the mRNA and protein levels of FXR,SHP1,SHP2,CYP7A1,and NTCP.Results Upon Tannin cloudy acid intervention,the mRNA and protein levels of FXR,SHP1,SHP2 were remarkably increased,and those of CYP7A1 and NTCP were reduced.After either up-or down-regulating FXR,Tannin cloudy acid could still increase the mRNA and protein levels of FXR,SHP1,and SHP2;and decrease the protein levels of CYP7A1 and NTCP,especially when administered at a high concentration.Conclusion Tannin cloudy acid exerts a protective effect on hepatocytes,and rescue the deleterious activities of intrahepatic cholestasis by stimulating FXR-associated pathways.

关 键 词：鞣料云实酸 LO2细胞 法尼酯衍生物X受体 胆汁淤积 

分 类 号：R575.6[医药卫生—消化系统] R972[医药卫生—内科学]