中药新药与临床药理2026，Vol.37Issue(4)：573-586,14.DOI:10.19378/j.issn.1003-9783.2026.04.001
益气续骨合剂调控Nrf2/GPX4信号通路对膝骨关节炎软骨细胞铁死亡的影响
Effects of Yiqi Xugu Mixture on Ferroptosis in Chondrocytes of Knee Osteoarthritis via Regulating the Nrf2/GPX4 Signaling Pathway
摘要
Abstract
Objective To investigate the effects and mechanism of Yiqi Xugu Mixture on knee osteoarthritis(KOA)through the Nrf2/GPX4 signaling pathway-mediated ferroptosis.Methods For the in vivo experiment,a KOA model was established in SD rats using the anterior cruciate ligament transection(ACLT)method.After intragastric administration of Yiqi Xugu Mixture,cartilage tissues were harvested.Histopathological staining was used to observe morphological changes in cartilage tissue;immunohistochemistry was employed to detect the expression of Nrf2,GPX4,SLC7A11,and ACSL4 in rat cartilage;and transmission electron microscopy was used to observe the ultrastructure of chondrocytes.For the in vitro experiment,chondrocytes from SD rats were used.A ferroptosis model was induced using tert-butyl hydroperoxide(TBHP).After intervention with the drug-containing serum of Yiqi Xugu Mixture,cell viability was assessed by CCK-8 assay and EDU fluorescent staining;ROS levels in chondrocytes were detected using the DCFH-DA fluorescent probe;immunofluorescence was used to examine the expression levels of Nrf2 and GPX4 in chondrocytes;mitochondrial membrane potential was measured with JC-1 staining;biochemical kits were used to determine Fe2+,MDA,and GSH levels in chondrocytes;and RT-qPCR and Western Blot were performed to measure the mRNA and protein expression levels of Nrf2,GPX4,SLC7A11,ACSL4,CollagenⅡ,and Aggrecan in chondrocytes.Results The in vivo results showed that,compared with the model group,Yiqi Xugu Mixture significantly alleviated mitochondrial damage in chondrocytes,improved cartilage tissue injury in the SD rat KOA model,and reduced the Mankin score(P＜0.05,P＜0.01).It upregulated the expression of Nrf2,GPX4,and SLC7A11 in cartilage tissue(P＜0.05,P＜0.01)and downregulated the expression of ACSL4(P＜0.05,P＜0.01).The in vitro results demonstrated that,compared with the model group,the drug-containing serum of Yiqi Xugu Mixture increased chondrocyte viability(P＜0.05,P＜0.01),downregulated the levels of ROS,Fe2+,and MDA in chondrocytes(P＜0.01),upregulated GSH levels(P＜0.01),restored mitochondrial membrane potential in chondrocytes(P＜0.01),upregulated the mRNA and protein expression of Nrf2,GPX4,SLC7A11,Collagen Ⅱ,and Aggrecan(P＜0.05,P＜0.01),and downregulated the mRNA and protein expression of ACSL4(P＜0.01).Conclusion Yiqi Xugu Mixture may alleviate cartilage injury in knee osteoarthritis by inhibiting chondrocyte ferroptosis through activation of the Nrf2/GPX4 signaling pathway.关键词
益气续骨合剂/Nrf2/GPX4 信号通路/膝骨关节炎/软骨细胞/铁死亡/大鼠Key words
Yiqi Xugu Mixture/Nrf2/GPX4 signaling pathway/knee osteoarthritis/chondrocytes/ferroptosis/rats分类
医药卫生引用本文复制引用
吴祖贵,朱月,李皎,刘金清,袁蓉,吴志伟,申震,董玮,郭英..益气续骨合剂调控Nrf2/GPX4信号通路对膝骨关节炎软骨细胞铁死亡的影响[J].中药新药与临床药理,2026,37(4):573-586,14.基金项目
国家自然科学基金项目(82360943) （82360943）
云南省科技厅项目(202101AZ070001-170,202301AZ070001-094,202301AZ070001-15,202501AZ070001-018,202501AZ070001-117) （202101AZ070001-170,202301AZ070001-094,202301AZ070001-15,202501AZ070001-018,202501AZ070001-117）
云南省基础研究专项(202501AU070167) （202501AU070167）
云南省临床医学中心科研项目(2024YNLCYXZX0293). （2024YNLCYXZX0293）
