Liao E, Liu Qiao-Qiao, Huang Xiao-Mei, Shao Yong
Department of Obstetrics and Gynecology, The First Affiliated Hospital of Chongqing Medical University, No. 1 of Youyi Road, Yuanjiagang, Daping Street, Yuzhong District, Chongqing, 400042, China.
Department of Obstetrics, Maternal and Child Health Hospital of Hubei Province, Wuhan, 430070, Hubei, China.
J Mol Histol. 2025 Mar 10;56(2):102. doi: 10.1007/s10735-025-10387-6.
Intrahepatic cholestasis of pregnancy (ICP) is a liver disease that manifests predominantly in the later stages of pregnancy. The primary treatment currently involves the use of ursodeoxycholic acid (UDCA). In this study, the therapeutic effectiveness of 4-phenylbutyric acid (4-PBA) in the treatment of ICP, as well as the potential mechanisms involved, are investigated to offer new references for clinical treatment decisions using ICP model. The therapeutic effect of 4-PBA on ICP was evaluated by drug therapy on ICP cells and animal models, and corresponding fluorescence immunoassay, electron microscope, WB and other experiments. In addition, the cells and animals treated with GPR30 inhibitor were treated to investigate whether 4-PBA promoted the expression of bile salt output pump (BSEP) protein through GPR30-PI3K pathway, thereby promoting bile acid excretion. Administration of 4-PBA significantly reduced the incidence of stillbirth associated with ICP. 4-PBA was effective in decreasing serum bile acid levels, reducing the activation of the GPR30-PI3K pathway, and increasing the expression of BSEP protein in hepatocytes. 4-PBA was effective in reducing bile acid levels and significantly improving fetal outcomes associated with ICP. The potential mechanism involves the promotion of BSEP localization and expression in the hepatocytes' microvilli structures via the GPR30-PI3K pathway.
妊娠期肝内胆汁淤积症（ICP）是一种主要在妊娠后期出现的肝脏疾病。目前的主要治疗方法是使用熊去氧胆酸（UDCA）。在本研究中，研究了4-苯基丁酸（4-PBA）治疗ICP的疗效及其潜在机制，为使用ICP模型进行临床治疗决策提供新的参考依据。通过对ICP细胞和动物模型进行药物治疗，并进行相应的荧光免疫测定、电子显微镜、WB等实验，评估4-PBA对ICP的治疗效果。此外，对用GPR30抑制剂处理的细胞和动物进行处理，以研究4-PBA是否通过GPR30-PI3K途径促进胆盐输出泵（BSEP）蛋白的表达，从而促进胆汁酸排泄。给予4-PBA可显著降低与ICP相关的死产发生率。4-PBA可有效降低血清胆汁酸水平，减少GPR30-PI3K途径的激活，并增加肝细胞中BSEP蛋白的表达。4-PBA可有效降低胆汁酸水平，并显著改善与ICP相关的胎儿结局。其潜在机制包括通过GPR30-PI3K途径促进BSEP在肝细胞微绒毛结构中的定位和表达。
