山西医科大学学报2025，Vol.56Issue(11)：1227-1233,7.DOI:10.13753/j.issn.1007-6611.2025.11.004
黄芪甲苷通过调控自噬抑制肝星状细胞活化
Astragaloside Ⅳ suppresses fibrogenesis by down-regulating autophagy-related proteins in hepatic stellate cells
摘要
Abstract
Objective To investigate the effects of Astragaloside Ⅳ(AS-Ⅳ)on autophagy and activation of hepatic stellate cells(HSCs)and its underlying mechanisms.Methods HSC-T6 cells were cultured in vitro and stimulated with platelet-derived growth factor-BB(PDGF-BB)to establish a liver fibrosis(HF)model.The successful establishment of HF model was confirmed by the overex-pression of fibrosis markers(α-SMA and α1-Collagen).To determine the optimal concentration of AS-Ⅳ intervention,HSC-T6 cells were divided into five groups:control group,HF group,HF+AS-Ⅳ 20 μmol/L group,HF+AS-Ⅳ 30 μmol/L group,and HF+AS-Ⅳ40 μmol/L group.To investigate the effect of AS-Ⅳ on autophagy,HSC-T6 cells were divided into three groups:control group,HF group,and HF+AS-Ⅳ(40 μmol/L)group.To explore the impact of autophagy activation on the anti-fibrotic effect of AS-Ⅳ,HSC-T6 cells were divided into four groups:control group,HF group,HF+AS-Ⅳ(40 μmol/L)group,and HF+AS-Ⅳ(40 μmol/L)+Rapamycin(RAPA)group.The mRNA expression levels of inflammatory factors TNF-α and TGF-β1 were detected by qRT-PCR,and the protein expressions of fibrosis-related markers(α-SMA,α1-Collagen)and autophagy-related markers(LC3-Ⅱ/LC3-Ⅰ,Beclin-1)were analyzed by Western blot.Results Compared to control group,the mRNA levels of TNF-α and TGF-β1 were significantly increased,and the protein expressions of α-SMA and α1-Collagen were alao increased(P<0.001).Compared to HF group,the mRNA levels of TNF-α and TGF-β1 were significantly decreased in HF+AS-Ⅳ(20,30,40 μmol/L)groups(P<0.001),and the expressions of α-SMA and α1-Collagen were significantly reduced(P<0.05),especially in HF+AS-Ⅳ(40 μmol/L)group(P<0.000 1).The ratio of LC3-Ⅱ/LC3-Ⅰand the expression of Beclin-1 were significantly lower in HF+AS-Ⅳ(40 μmol/L)group than in HF group(P<0.05).Compared to HF+AS-Ⅳ(40 μmol/L)group,LC3-Ⅱ/LC3-Ⅰ ratio,and the expressions of Beclin-1,α-SMA,α1-Collagen,TNF-α and TGF-β1 were up-regulated in HF+AS-Ⅳ(40 μmol/L)+RAPA group(P<0.05).Conclusion AS-Ⅳ may inhibit the activation of HSCs and improve the liver fibrosis by down-regulating the expressions of autophagy-related proteins LC3-Ⅱ and Beclin-1.关键词
黄芪甲苷/肝星状细胞/自噬/肝纤维化/炎症因子/雷帕霉素Key words
Astragaloside Ⅳ/hepatic stellate cells/autophagy/hepatic fibrosis/inflammatory factors/Rapamycin分类
医药卫生引用本文复制引用
LI Tian,HOU Mingsu,LI Xiaofeng,SONG Yanrong..黄芪甲苷通过调控自噬抑制肝星状细胞活化[J].山西医科大学学报,2025,56(11):1227-1233,7.基金项目
山西省卫生健康委员会科研课题(2023018) （2023018）
