安徽医科大学学报2026，Vol.61Issue(7)：1183-1190,8.DOI:10.19405/j.cnki.issn1000-1492.2026.07.004
4-苯基丁酸改善脂多糖引起的母鼠胆汁酸代谢紊乱
4-Phenylbutyrate ameliorates lipopolysaccharide-induced bile acid metabolism disorder in maternal mice
摘要
Abstract
Objective To explore the ameliorative effect of the endoplasmic reticulum stress inhibitor 4-phenylbu-tyric acid(4-PBA)on bile acid metabolism disorders induced by bacterial lipopolysaccharide(LPS)in late-pregnant mice,and to clarify the regulatory mechanism of endoplasmic reticulum stress(ERS)in intrahepatic cho-lestasis of pregnancy(ICP).Methods Twenty-four pregnant mice were divided into control group,LPS group,4-PBA group,and LPS+4-PBA group.On the 16th day of pregnancy,the LPS group received intraperitoneal injec-tion of LPS(200 μg/kg)and the 4-PBA group received injection of 4-PBA(150 mg/kg).In the LPS+4-PBA group,4-PBA was intraperitoneally injected first,followed by LPS administration 1 h later.Serum total bile acid(TBA),liver injury markers,bile acid profiles,and the expression of key genes and proteins were detected 6 h af-ter LPS treatment.Results LPS exposure increased serum TBA levels in pregnant mice(P＜0.05),activated ERS markers and inflammatory factors,and downregulated bile acid transporters and the expression of the rate limiting enzyme CYP7A1(all P＜0.05).4-PBA intervention effectively inhibited ERS,reduced TBA levels(P＜0.05),and upregulated Ntcp,Bsep,Mdr3,and Mrp3 gene expression(all P＜0.05).Conclusion ERS plays an important role in LPS interference with the homeostasis of bile acid metabolism during pregnancy.Inhibiting ERS can im-prove bile stasis by regulating bile acid transporters,providing a theoretical basis for targeted therapy of ICP.关键词
妊娠期肝内胆汁淤积症/内质网应激/细菌脂多糖/4-苯基丁酸/胆汁酸代谢/肝脏Key words
intrahepatic cholestasis of pregnancy/endoplasmic reticulum stress/lipopolysaccharide/4-Phenyl-butyric acid/bile acid metabolism/liver分类
医药卫生引用本文复制引用
梁心茹,孙影,暴双蕊,詹童,吴红艳,陶文康,张伦,王建青,张程..4-苯基丁酸改善脂多糖引起的母鼠胆汁酸代谢紊乱[J].安徽医科大学学报,2026,61(7):1183-1190,8.基金项目
国家自然科学基金项目(编号:82073566) （编号:82073566）
安徽省自然科学基金项目(编号:2008085MH280) （编号:2008085MH280）
安徽省高校中青年教师培养行动项目(编号:DTR2023012) National Natural Science Foundation of China(No.82073566) （编号:DTR2023012）
Natural Science Foundation of Anhui Province(No.2008085MH280) （No.2008085MH280）
Project for Cultivation of Young and Middle-aged Teachers in Univerisi-ties of Anhui Province(No.DTR2023012) （No.DTR2023012）
