中国药房2026，Vol.37Issue(8)：1027-1032,6.DOI:10.6039/j.issn.1001-0408.2026.08.10
骨碎补总黄酮调控Notch1/Hes1信号轴促进软骨细胞自噬并抑制凋亡的机制研究
Regulation of Notch1/Hes1 signaling axis by total flavonoids of Drynariae Rhizoma for promoting chondrocyte autophagy and inhibiting apoptosis:a mechanistic study
摘要
Abstract
OBJECTIVE To investigate the effects of total flavonoids of Drynariae Rhizoma(TFRD)on autophagy and apoptosis in LPS-induced chondrocytes via the regulation of the Notch1/hairy and enhancer of split 1(Notch1/Hes1)signaling axis.METHODS Human chondrocyte cell line C28/I2 cells were cultured with 5 μg/mL LPS to establish in vitro inflammatory injury model.The cells were separated into normal control group,model group,TFRD group(200 μg/mL),TFRD+peroxiredoxin 1(Prdx1)small interfering RNA(si-Prdx1)group and TFRD+si-Prdx1 negative control(si-NC)group,with 6 replicate wells in each group.Cells were transfected with si-Prdx1 or si-NC for 24 hours,pretreated with TFRD for 2 hours,and then exposed to LPS,with a total culture duration of 48 hours.Apoptotic rate,the proportion of apoptotic cells,monodansylcadaverine(MDC)fluorescence intensity,as well as the contents of matrix metalloproteinase-13(MMP-13),a disintegrin and metalloproteinase with thrombospondin motifs 5(ADAMTS5),and cartilage oligomeric matrix protein(COMP)were measured.Additionally,the protein expression levels of X-linked inhibitor of apoptosis protein(XIAP),poly(ADP-ribose)polymerase 1(PARP1),Beclin-1,microtubule-associated protein 1 light chain 3 Ⅱ/Ⅰ(LC3-Ⅱ/Ⅰ),PTEN-induced putative kinase 1(PINK1),Notch1,Hes1,and Prdx1 were assessed.RESULTS Compared with model group,the apoptotic rate,the proportion of apoptotic cells,the contents of MMP-13 and ADAMTS5 as well as protein expressions of PARP1 were significantly decreased,while MDC fluorescence intensity,COMP content,protein expressions of XIAP,Beclin-1,LC3-Ⅱ/Ⅰ,PINK1,Notch1,Hes1 and Prdx1 were significantly increased(P<0.05).Compared with TFRD+si-NC group,the changes in the aforementioned indicators(except for Notch1 and Hes1)in the cells of the TFRD+si-Prdx1 group were significantly reversed(P<0.05).CONCLUSIONS TFRD may activate the Notch1/Hes1 signaling axis,and up-regulate the expression of the downstream target molecule Prdx1,thereby inhibiting LPS-induced chondrocyte apoptosis,promoting protective autophagy,and consequently improving cartilage metabolic homeostasis.关键词
骨碎补总黄酮/软骨细胞/Notch受体1/Hes1信号轴/自噬/凋亡Key words
total flavonoids of Drynariae Rhizoma/chondrocyte/Notch1/Hes1 signaling axis/autophagy/apoptosis分类
医药卫生引用本文复制引用
鲁林,方虹..骨碎补总黄酮调控Notch1/Hes1信号轴促进软骨细胞自噬并抑制凋亡的机制研究[J].中国药房,2026,37(8):1027-1032,6.基金项目
湖北省中医药管理局中医药科研项目(No.ZY2025L063) （No.ZY2025L063）
