中草药2026，Vol.57Issue(18)：7192-7204,13.DOI:10.7501/j.issn.0253-2670.2026.18.010
养肝软坚丸防治肝纤维化作用及机制
Effect and mechanism of Yanggan Ruanjian Wan in prevention and treatment of hepatic fibrosis
摘要
Abstract
Objective To explore the effect and mechanism of Yanggan Ruanjian Wan(养肝软坚丸,YGRJW)in prevention and treatment of hepatic fibrosis(HF)based on in vivo and in vivo experiments and transcriptome sequencing technology.Methods LX-2 cell activation model was induced by transforming growth factor-βi(TGF-β1),CCK-8 method,cell scratch assay,qRT-PCR and Western blotting were used to detect the effects of YGRJW-medicated serum on cell viability,proliferation,expressions of inflammatory cytokines[interleukin-1β(IL-1β),IL-6,tumor necrosis factor-α(TNF-α)]and fibrosis markers[α-smooth muscle actin(α-SMA),collagen type 1 alpha 1 chain(COL1A1),collagen type Ⅲ alpha 1 chain(COL3A1)].Transcriptome sequencing was employed to identify differentially expressed genes and key pathways in activated LX-2 cells treated with YGRJW-containing serum,followed by validation through qRT-PCR and immunofluorescence experiments.A HF model was induced in mice via intraperitoneal injection of a 10％carbon tetrachloride(CCl4)-containing corn oil solution.After drug intervention,the therapeutic effects of YGRJW on HF mice were comprehensively evaluated by measuring body weight,organ indices,liver and kidney function,pathological changes in liver tissue,expressions of inflammatory factors and fibrosis markers in liver tissue,as well as levels of inflammatory factors and four liver fibrosis indicators in serum,while also verifying the effect of YGRJW on potential pharmacodynamic targets and key pathway indicators.Results In vitro experiments demonstrated that 10％YGRJW-containing serum significantly inhibited LX-2 cell activation after 24 h(P＜0.01)and downregulated mRNA expression levels of inflammatory factors and fibrosis markers(P＜0.05,0.01,0.001),with superior inhibitory effects compared to 10％silybinin-containing serum.Transcriptomic analysis and validation results showed that YGRJW may exert anti-HF effects through the colony stimulating factor 3 receptor(CSF3R)/Janus kinase 2(JAK2)/signal transducer and activator of transcription 3(STAT3)pathway.Compared with model group,YGRJW drug containing serum intervention could significantly downregulate the mRNA and protein expressions of CSF3R,JAK2 and STAT3(P＜0.05,0.01).The in vivo experimental results showed that YGRJW could significantly improve the slow growth of body weight in HF mice(P＜0.05),reduce liver index,spleen index,liver and kidney function indicators(P＜0.05,0.01,0.001),alleviate liver tissue inflammation infiltration and collagen deposition,reduce the mRNA expression levels of TGF-β,TNF-α,IL-6,α-SMA,COL1A1,COL3A1 and tissue inhibitor of metalloproteinases-1(TIMP-1)in liver tissue(P＜0.05,0.01,0.001),increase the mRNA expression level of fibroblast growth factor 7(FGF7)(P＜0.05,0.01),and reduce levels of inflammatory factors and four indicators of liver fibrosis in serum(P＜0.05,0.01,0.001),and downregulated mRNA and protein expressions of CSF3R,JAK2,STAT3 in liver tissue(P＜0.05,0.01).Conclusion YGRJW exerts anti-HF effects by regulating CSF3R/JAK2/STAT3 signaling pathway,to inhibit hepatic stellate cell(HSC)activation and reducing extracellular matrix(ECM)deposition.关键词
养肝软坚丸/肝纤维化/CSF3R/JAK2/STAT3信号通路/肝星状细胞活化/细胞外基质代谢Key words
Yanggan Ruanjian Wan/hepatic fibrosis/CSF3R/JAK2/STAT3 signaling pathway/hepatic stellate cell activation/extracellular matrix metabolism分类
医药卫生引用本文复制引用
杨泽虹,赵利娜,陈昫,李培武,刘菀尧,苏炜炫,林瑛乔,梁水先,文艺,洪日,丘振文,孙术宁..养肝软坚丸防治肝纤维化作用及机制[J].中草药,2026,57(18):7192-7204,13.基金项目
广州中医药大学"固本"工程一级学科能力提升项目(广中医校办[2026]105号) （广中医校办[2026]105号）
广东省中医药局科研项目(20261121) （20261121）
国家中医药传承创新中心科研专项重点项目(2023ZD07) （2023ZD07）
邝卫红省名中医工作室(粤府函[2023]16号) （粤府函[2023]16号）
