湖北科技学院学报（医学版）2025，Vol.39Issue(6)：502-506,5.DOI:10.16751/j.cnki.2095-4646.2025032004
FXR/SHP通路介导依折麦布改善草甘膦诱导性肝损伤的机制
The FXR/SHP Pathway Mediates the Mechanism by which Ezetimibe Ameliorates Glyphosate-Induced Hepatotoxicity
摘要
Abstract
Objective To investigate the mechanism by which ezetimibe(EZ)ameliorates glyphosate(GLY)-induced liver injury in mice by regulating the FXR/SHP pathway.Methods Male C57BL/6 mice were randomly divided into four groups:control(CON),glypho-sate-exposed(GLY),EZ-treated(EZ),and GLY+EZ co-treated(GLY+EZ)groups.After 42-day oral administration,biochemical parame-ters of liver function(TC,TG,HDL,LDL,TBA,ALT,AST,ALP)were measured.Hepatic histopathological alterations were evaluated via HE staining.Quantitative real-time PCR(qRT-PCR)was performed to assess FXR,SHP,and CYP7A1 mRNA expression levels in liver tissues.Molecular docking was utilized to analyze the binding affinity between EZ and FXR/SHP.Results Compared with the CON group,the GLY group exhibited significantly increased hepatic index,hepatic LDL,and ALT levels,while TBA levels were reduced(all P＜0.01).Histolog-ical analysis revealed the typical features of liver injury in the GLY group,including disorganized liver lobule structure with sinusoidal con-gestion and hepatocyte swelling,as well as downregulated FXR and CYP7A1 mRNA expression and upregulated SHP mRNA levels.Co-treat-ment with EZ significantly attenuated hepatic index,ALT,AST,and ALP activity(P＜0.05),restored TBA levels,and mitigated histological damage.Molecular docking showed that the binding energies of EZ with FXR and SHP were-1.6 and-2.0 kcal/mol,respectively,both less than 0,suggesting binding activity.Conclusion EZ alleviates GLY-induced hepatotoxicity potentially by regulating the FXR/SHP path-way,providing a novel protective mechanism against environmental toxicant-induced liver injury and pharmacological insights for therapeutic intervention.关键词
草甘膦/依折麦布/肝损伤/分子对接/FXR/SHP通路Key words
Glyphosate/Ezetimibe/Liver injury/Molecular docking/FXR/SHP pathway分类
医药卫生引用本文复制引用
徐旭龙,赵雪,沈昕,王贝贝,张晓琳,晏彪..FXR/SHP通路介导依折麦布改善草甘膦诱导性肝损伤的机制[J].湖北科技学院学报（医学版）,2025,39(6):502-506,5.基金项目
湖北省自然科学基金青年项目(2023AFB478) （2023AFB478）
国家自然科学基金青年项目(42307547) （42307547）
