中国临床药理学与治疗学2026，Vol.31Issue(2)：204-212,9.DOI:10.12092/j.issn.1009-2501.2026.02.008
基于CYP7A1/FXR/SHP途径探究大黄素对胆汁淤积性肝损伤小鼠的治疗作用
Therapeutic effect of emodin on cholestatic liver injury in mice based on CYP7A1/FXR/SHP pathway
摘要
Abstract
AIM:To investigate the therapeutic ef-fect of emodin on cholestatic liver injury in mice.METHODS:C57BL/6J mice were subcutaneously in-jected with ethinyl estradiol(EE)for 7 consecutive days to establish a cholestasis model.The changes of body weight and serum levels of alanine amino-transferase(ALT),aspartate aminotransferase(AST),γ-glutamyl transpeptidase(γ-GT)and total bilirubin(TBIL)were detected.HE(hematoxylin-eosin)staining and MASSON staining were used to evaluate the effects on liver and other organs.Af-ter the efficacy was determined by animal model administration experiment,the human normal liver cell L02 was induced by lithocholic acid(LCA)to construct a cholestatic cell model.The CCK-8 method was used to detect the median lethal dose(IC50)by LCA intervention for 24 hours to determine the modeling concentration.Through emodin inter-vention for 24 h,the survival rate of each group was detected to determine the concentration of emodin.The survival rate of emodin on liver cells after LCA modeling was detected and evaluated.By detecting the changes of liver injury index related enzymes ALT,AST levels and oxidative stress relat-ed enzymes glutathione(GSH),serum superoxide dismutase(SOD),malondialdehyde(MDA)and reac-tive oxygen species(ROS)levels in each group of L02 cells,the mechanism of emodin in anti-cholestasis by improving oxidative stress was evaluated.West-ern blot was used to detect the protein expression of Cholesterol 7α-hydroxylase(CYP7A1),Farnesol X receptor(FXR)and small heterodimer partner(SHP)in the liver of mice.RESULTS:Emodin significantly improved the body weight change and liver index of mice,reduced the levels of ALT,AST,γ-GT and TBIL in serum,improved the trend of liver lesions,and inhibited liver damage.Improving the survival rate of L02 cells improved the survival state of cells,re-duced the changes of ALT and AST levels and im-proved cell damage.It also changed the level of ox-idative stress by increasing GSH and SOD levels and reducing MDA and ROS levels.In addition,emodin significantly increased FXR and SHP in the liver of mice and decreased the protein expression level of CYP7A1.CONCLUSION:Emodin can play a protec-tive role in cholestatic liver injury,and its mecha-nism may be through inhibiting oxidative stress in-jury and regulating bile acid synthesis and metabolism through FXR/CYP7A1/SHP pathway.关键词
大黄素/胆汁淤积/肝损伤/氧化应激Key words
emodin/cholestasis/liver injury/ox-idative stress分类
医药卫生引用本文复制引用
王玮辰,马雅萍,王萌,李庆林,程卉..基于CYP7A1/FXR/SHP途径探究大黄素对胆汁淤积性肝损伤小鼠的治疗作用[J].中国临床药理学与治疗学,2026,31(2):204-212,9.基金项目
安徽省高校自然科学研究重点项目(KJ2021A0591 （）
2022AH050529) （）
国家自然科学青年基金项目(82305023) （82305023）
