海南医科大学学报2025，Vol.31Issue(11)：808-815,8.DOI:10.13210/j.cnki.jhmu.20250208.005
基于树突状细胞成熟分化探讨ω-鼠胆酸抑制肝纤维化的机制研究
Mechanism of ω-muricholic acid ameliorating liver fibrosis by inhibiting dendritic cell maturation
摘要
Abstract
Objective:To investigate the effects of ω-muricholic acid(ω-MCA)on the FXR/LKB1/NF-κB signaling pathway in dendritic cells(DCs)and elucidate its molecular mechanisms in inhibiting DC maturation and subsequently liver fibrosis.Meth-ods:Murine myeloid dendritic cells were isolated and a maturation model was established by inducing with LPS.ω-MCA was ad-ministered as an intervention.Flow cytometry and Western blot were used to detect the expression of surface marker molecules(CD40,CD80,and MHC-Ⅱ)and proteins related to the FXR/LKB1/NF-κB signaling pathway.CD4+T lymphocytes were iso-lated and co-cultured with DCs.Flow cytometry and ELISA were employed to measure the expression of Foxp3 in CD4+T lym-phocytes and the levels of inflammatory cytokines(IL-10 and TGF-β1).CD4+T lymphocytes were co-cultured with the hepatic stellate cell line JS1,and flow cytometry and Western blot were used to assess JS1 apoptosis and the expression of α-SMA protein.Results:Compared to the model group,ω-MCA significantly inhibited the expression of surface molecules CD40,CD80,and MHC-Ⅱ in DCs,upregulated the expression of FXR,LKB1,and p65 proteins,and decreased the ratio of p-p65/total-p65,all with statistically significant differences(P<0.01).Additionally,ω-MCA significantly increased the proportion of Tregs and the anti-inflammatory cytokine IL-10 in naive CD4+T cells,while inhibiting the secretion of TGF-β1,with statistically significant dif-ferences compared to the model group(P<0.01).Furthermore,ω-MCA significantly suppressed the apoptosis level and α-SMA protein expression in JS1 cells,with statistically significant differences(P<0.01).Conclusion:ω-MCA exerts an anti-fibrotic ef-fect by inhibiting the activation of the FXR/LKB1/NF-κB signaling pathway,thereby repressing the maturation and differentiation of dendritic cells and subsequently inhibiting the activation of hepatic stellate cells.关键词
胆汁酸/ω-鼠胆酸/树突状细胞/肝星状细胞/肝纤维化Key words
Bile acids/ω-muricholic acid/Dendritic cells/Hepatic stellate cells/Liver fibrosis分类
医药卫生引用本文复制引用
杨柳欣,高婷婷,王炳予,袁星星..基于树突状细胞成熟分化探讨ω-鼠胆酸抑制肝纤维化的机制研究[J].海南医科大学学报,2025,31(11):808-815,8.基金项目
This study was supported by Scientific Research Project of Heilongjiang Provincial Health Commission(20222121020595) （20222121020595）
Natural Science Foundation of Heilongjiang Province Outstanding Youth Project(YQ2022H015) 黑龙江省卫生健康委科研项目(20222121020595) （YQ2022H015）
黑龙江省自然科学基金优秀青年项目(YQ2022H015) （YQ2022H015）
