亚太传统医药2025，Vol.21Issue(3)：16-21,6.DOI:10.11954/ytctyy.202503003
雷公藤红素抑制TNF-α诱导的类风湿关节炎作用及其机制研究
Study on the Inhibitory Effect and Mechanism of Celastrol Against Rheumatoid Arthritis Induced by TNF-α
摘要
Abstract
Objective:To explore the effect and mechanism of Celastrol in inhibiting tumor necrosis factor-alpha(TNF-α)induced rheumatoid arthritis.Methods:An in vitro rheumatoid arthritis model was established using human rheumatoid arthritis fibroblast-like synoviocytes(RA-FLS)MH7A.The groups were divided into a blank group,a model group(TNF-α 10 ng/mL),and a treatment group.MH7A cells treated with high-glucose DMEM culture medi-um containing 10％fetal bovine serum and 1％penicillin-streptomycin mixture served as the control group.MH7A cells were treated with a final concentration of 10 ng/mL TNF-α for 24 hours as the model group.MH7A cells were treated with a series of concentrations of Celastrol for 2 hours followed by a final concentration of 10 ng/mL TNF-α for 24 hours as the treatment group.The cytotoxicity of Celastrol on MH7A was detected using the CCK-8 assay,and the in-hibitory activity of Celastrol on the abnormal proliferation of TNF-α induced RA-FLS synovial inflammatory cells was detected.The expression of interleukin-1 beta(IL-1β)and interleukin-6(IL-6)and matrix metalloproteinases(MMP-1 and MMP-3)produced by RA-FLS was measured using the enzyme-linked immunosorbent assay(ELISA).The expres-sion of apoptosis-related proteins and mechanism-related proteins in RA-FLS was detected by Western blot.Results:Compared to the control group,the model group showed a significant increase in inflammatory cytokines(P＜0.01)and ma-trix metalloproteinases after being activated by TNF-α(P＜0.000 1).The proliferation of RA-FLS in the drug groups was significantly inhibited(P＜0.001),and the expression of IL-1β,IL-6,MMP-1,and MMP-3 was also significantly reduced compared to the model group.Celastrol treatment inhibited the activation of phosphorylated ERK pathway proteins(P＜0.01)and promoted apoptosis in RA-FLS(P＜0.05).Conclusion:The mechanism by which Celastrol inhibits tumor necrosis factor-alpha(TNF-α)induced rheumatoid arthritis may be related to its inhibition of the activation of phosphorylated extracellular signal-regulated kinase(ERK)pathway proteins,which promotes the apoptosis of rheumatoid arthritis fibroblast-like synovio-cytes(RA-FLS).关键词
类风湿关节炎/类风湿关节炎成纤维样滑膜细胞/雷公藤红素/肿瘤坏死因子α/凋亡/ERKKey words
Rheumatoid Arthritis/Rheumatoid Arthritis Human Fibroblast-Like Synovial Cell/Celastrol/Tumor Necro-sis Factor α/Apoptosis/ERK分类
医药卫生引用本文复制引用
李科,曹玉净,钱亚男,李光辉,周松林..雷公藤红素抑制TNF-α诱导的类风湿关节炎作用及其机制研究[J].亚太传统医药,2025,21(3):16-21,6.基金项目
国家自然科学基金项目(82104833) （82104833）
河南省中医药科学研究专项课题(2024ZYZD06,2023ZY1008,2019ZYBJ15) （2024ZYZD06,2023ZY1008,2019ZYBJ15）
