4-苯基丁酸改善脂多糖引起的母鼠胆汁酸代谢紊乱OA

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.