海南医科大学学报2025，Vol.31Issue(14)：1077-1085,1094,10.DOI:10.13210/j.cnki.jhmu.20250609.002
基于FXR/LKB1/NF-κB信号通路介导的树突状细胞成熟分化探讨芪参汤抑制肝纤维化的机制研究
Qishen decoction inhibits liver fibrosis by regulating FXR/LKB1/NF-κB signaling pathway mediated dendritic cell maturation
摘要
Abstract
Objective:This study aims to investigate the effects of Qishen decoction on the FXR/LKB1/NF-κB signaling pathway-mediated maturation and differentiation of dendritic cells and to elucidate its molecular mechanism in inhibiting the activa-tion of hepatic stellate cells for the treatment of liver fibrosis.Methods:Mouse bone marrow-derived dendritic cells were isolated,and a maturation model was constructed using lipopolysaccharide.The cells were treated with either ω-muricholic acid(ω-MCA)or Qishen decoction-containing serum.Flow cytometry was employed to detect the expression levels of CD40,CD80,and MHC-II on dendritic cells.Western blot and RT-qPCR were used to analyze the expression of FXR/LKB1/NF-κB signaling path-way related molecules.Furthermore,co-culture experiments were conducted between dendritic cells and naive CD4+T cells,as well as between naive CD4+T cells and hepatic stellate cells(JS1).Flow cytometry was used to assess the differentiation of naive CD4+T cells into regulatory T cells(Tregs)and the apoptosis of JS1 cells.Enzyme-linked immunosorbent assays(ELISA)were performed to measure the levels of interleukin-10(IL-10)and transforming growth factor-β(TGF-β)in the supernatants of naive CD4+T cells.CCK-8 assays and Western blot were used to evaluate the proliferation activity and α-smooth muscle actin(α-SMA)protein expression of JS1 cells.Results:Compared to the model group,drug intervention significantly inhibited the ex-pression of CD40,CD80,and MHC-II,upregulated the expression of FXR and LKB1 proteins and mRNA,reduced the ratio of phosphorylated P65 to total P65,increased the expression of P65 protein in the cytoplasm,and inhibited the distribution of P65 protein in the nucleus in dendritic cells,with all differences being statistically significant(P<0.01).Additionally,the co-culture results showed that compared to the model group,the percentage of Tregs,IL-10,and TGF-β levels in the ω-MCA,Qishen,and Qishen decoction combined with ω-MCA groups were significantly increased,while the apoptosis of JS1 cells,cell viability,and α-SMA protein expression were significantly reduced,with all differences being statistically significant(P<0.01).Conclu-sion:Qishen decoction inhibits the activation of the FXR/LKB1/NF-κB signaling pathway,thereby suppressing the maturation of dendritic cells,which in turn inhibits the activation of hepatic stellate cells and ameliorates liver fibrosis.This study provides new insights and potential therapeutic strategies for the treatment of liver fibrosis.关键词
芪参汤/肝纤维化/树突状细胞/初始CD4+T细胞/肝星状细胞Key words
Qishen decoction/Liver fibrosis/Dendritic cells/Naive CD4+T cells/Hepatic stellate cells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FXR/LKB1/NF-κB信号通路介导的树突状细胞成熟分化探讨芪参汤抑制肝纤维化的机制研究[J].海南医科大学学报,2025,31(14):1077-1085,1094,10.基金项目
This study was supported by the Excellent Youth Project of Heilongjiang Provincial Natural Science Foundation(YQ2022H015) 黑龙江省自然科学基金优秀青年项目(YQ2022H015) （YQ2022H015）
