湖北科技学院学报（医学版）2025，Vol.39Issue(5)：374-379,6.DOI:10.16751/j.cnki.2095-4646.2025032010
草甘膦经LRH-1/SR-B1通路加重小鼠胆固醇结石的机制
Glyphosate Exacerbated Mouse Cholesterol Gallstones via the LRH-1/SR-B1 Pathway
摘要
Abstract
Objective To investigate the exacerbating effect of glyphosate on cholesterol gallstone and elucidate its underlying mech-anisms.Methods The experimental protocol was conducted on male C57BL/6 mice,in which a lithogenic diet was administered to establish a cholesterol gallstone disease model.Mice were randomly allocated into four groups:normal control(CON),glyphosate-exposed(GLY),cholesterol stone model(CS),and combined model+glyphosate(CS+GLY)groups,with a 6-week experimental duration.Parameters eval-uated included body weight changes and gallstone formation status.Serum biochemical profiles were quantified,and hepatic and gallbladder tissues were conducted by Hematoxylin-Eosin(HE)staining.The transcriptional levels of cholesterol metabolism-associated genes in hepatic tissue were analyzed by quantitative real-time polymerase chain reaction(RT-qPCR).The binding affinities between glyphosate and choles-terol gallstone-related molecular targets were predicted by molecular docking simulations.Results The CS+GLY group exhibited accelerated body mass gain,gallstone occurrence,and significantly elevated serum ALT,AST,TC,and LDL-C levels(vs.CS,P＜0.01),indicating exac-erbated dyslipidemia.Histopathological analysis revealed distinct pathological alterations in the CS+GLY group,characterized by hepatocyte hypertrophy,enlargement of central venous lumina in hepatic lobules,and thickening of gallbladder mucosa.RT-qPCR results showed that the down-regulated hepatic FXR mRNA level,and upregulated LRH-1 and SR-B1 mRNA levels in CS+GLY group(vs.CS,P＜0.01).Molecu-lar docking confirmed robust binding interactions between glyphosate and FXR/LRH-1/SR-B1,with binding energies of-10.46,-5.10,-9.29kJ/mol,respectively.Conclusion Glyphosate can aggravate cholesterol gallstone pathogenesis through inhibiting FXR expression in liver tissue,thereby interfering with the LRH-1/SR-B1 pathway,resulting in abnormal serum lipid metabolism and liver and hepatobiliary damage.关键词
草甘膦/胆固醇结石病/FXR/LRH-1/SR-B1Key words
Glyphosate/Cholesterol gallstones/FXR/LRH-1/SR-B1分类
医药卫生引用本文复制引用
王贝贝,赵雪,徐旭龙,张晓琳,晏彪..草甘膦经LRH-1/SR-B1通路加重小鼠胆固醇结石的机制[J].湖北科技学院学报（医学版）,2025,39(5):374-379,6.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）
