4-Phenylbutyrate ameliorates lipopolysaccharide-induced bile acid metabolism disorder in maternal mice
10.19405/j.cnki.issn1000–1492.2026.07.004
- VernacularTitle:4-苯基丁酸改善脂多糖引起的母鼠胆汁酸代谢紊乱
- Author:
Xinru LIANG
1
;
Ying SUN
1
;
Shuangrui BAO
1
;
Tong ZHAN
1
;
Hongyan WU
1
;
Wenkang TAO
2
;
Lun ZHANG
3
;
Jianqing WANG
2
;
Cheng ZHANG
1
Author Information
1. Department of Toxicology， School of Public Health， Anhui Medical University， Hefei 230032
2. School of Pharmacy， Anhui Medical University，Hefei 230032
3. Anhui Public Health Clinical Center， Hefei 230032
- Publication Type:Journal Article
- Keywords:
intrahepatic cholestasis of pregnancy;
endoplasmic reticulum stress;
lipopolysaccharide;
4-Phenylbutyric acid;
bile acid metabolism;
liver
- From:
Acta Universitatis Medicinalis Anhui
2026;61(7):1183-1190
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo explore the ameliorative effect of the endoplasmic reticulum stress inhibitor 4-phenylbutyric 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 cholestasis of pregnancy （ICP）. MethodsTwenty-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 injection 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 after LPS treatment. ResultsLPS 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）. ConclusionERS plays an important role in LPS interference with the homeostasis of bile acid metabolism during pregnancy. Inhibiting ERS can improve bile stasis by regulating bile acid transporters， providing a theoretical basis for targeted therapy of ICP.
