中医药导报2025，Vol.31Issue(9)：17-23,7.DOI:10.13862/j.cn43-1446/r.2025.09.003
淫羊藿苷调控Nrf2/HO-1信号通路对软骨细胞铁死亡的影响
Icariin Regulates Nrf2/HO-1 Signaling Pathway Mediated Chondrocyte Ferroptosis in the Treatment of Knee Osteoarthritis
摘要
Abstract
Objective:To explore the effect of icariin on the ferroptosis status of Atdc5 chondrocytes and its underlying mechanisms.Methods:In vitro culture of chondrocytes was performed to assess the effect of icariin at concentrations of 0.0,1.0,2.0,4.0,8.0,16.0,32.0 and 64.0 μmol/L on the proliferation of Atdc5 chondrocytes using the CCK-8 method,in order to determine the optimal intervention concentration.The Atdc5 chondrocytes were divided into blank control group,model group,low concentration icariin group,and high concentration icariin group.The blank control group did not receive any drug intervention,while the model group was treated with IL-1β(10 ng/mL).The low concentration icariin group was treated with IL-1β(10ng/mL)and icariin(8.0 μmol/L),and the high concentration icariin group received IL-1β(10 ng/mL)and icariin(16.0 μmol/L).All groups were treated for 24 hours.Fluorescence microscopy was used to detect the fluorescence intensity of the cells,and analyze the content of reactive oxygen species(ROS).A kit was utilized to measure the levels of malondialdehyde(MDA)and glutathione peroxidase(GSH-Px).Quantitative reverse transcription polymerase chain reaction(qRT-PCR)was employed to investigate the expression levels of type Ⅱ collagen α1 chain(COL2A1)mRNA,aggrecan(ACAN)mRNA,glutathione peroxidase 4(GPX4)mRNA,solute carrier family 7 member 11(SLC7A11)mRNA,nuclear factor erythroid 2-related factor 2(Nrf2)mRNA,and heme oxygenase 1(HO-1)mRNA.Additionally,protein expression levels of Nrf2,HO-1,GPX4,and SLC7A11 in the cells were assessed using Western blotting.Results:The concentrations of 8.0 μmol/L and 16.0μmol/L of icariin demonstrated no cytotoxicity to Atdc5 chondrocytes and significantly promoted their proliferation(P＜0.01),with similar effects on cell prolif-eration between the 8.0 μmol/L and 16.0 μmol/L groups(P＞0.05).The model group showed higher levels of ROS and MDA than blank control group(P＜0.01),while lower levels of GSH-Px than blank control group(P＜0.01).The low and high concentration icariin groups showed lower levels of ROS and MDA than model group(P＜0.01),while higher levels of GSH-Px than model group(P＜0.01).The model group showed lower relative expression levels of COL2A1 mRNA,ACAN mRNA,GPX4 mRNA,SLC7A11 mRNA,Nrf2 mRNA,and HO-1 mRNA than blank control group(P＜0.01).In contrast,the low and high concentration icariin groups showed higher relative expression levels of COL2A1 mRNA,ACAN mRNA,GPX4 mRNA,SLC7A11 mRNA,Nrf2 mRNA,and HO-1 mRNA than model group(P＜0.01).Additionally,the high concentration icariin group showed higher relative expression levels of COL2A1 mRNA and ACAN mRNA than low concentration icariin group(P＜0.05).The model group showed lower relative expression levels of Nrf2,HO-1,GPX4,and SLC7A11 proteins than blank control group(P＜0.01).The low and high concentration icariin groups showed higher relative expression levels of Nrf2,HO-1,GPX4,and SLC7A11 proteins than model group(P＜0.01).The high concentration icariin group showed higher relative expression levels of Nrf2 and HO-1 protein than low concentration icariin group(P＜0.01).Conclusion:Icariin may inhibit ferroptosis in chondrocytes and improve their functional status by activating the Nrf2/HO-1 antioxidant signaling pathway.关键词
膝骨关节炎/淫羊藿苷/软骨细胞/铁死亡/Nrf2/HO-1信号通路Key words
knee osteoarthritis/Icariin/chondrocyte/ferroptosis/Nrf2/HO-1 signaling pathway分类
医药卫生引用本文复制引用
张阔,张镭潇,郑泽炜,徐金凡,张庆文..淫羊藿苷调控Nrf2/HO-1信号通路对软骨细胞铁死亡的影响[J].中医药导报,2025,31(9):17-23,7.基金项目
广州市科技计划项目(2024A04J5057) （2024A04J5057）
广州中医药大学第三附属医院科研创新基金课题(Sy2022002) （Sy2022002）
广东省中医药局项目(20223012) （20223012）
