中药药理与临床2025,Vol.41Issue(5):22-27,6.
栀子苷调节TLR4/MyD88/NF-κB信号通路缓解膝骨关节炎大鼠的炎症反应
Geniposide Regulates TLR4/MyD88/NF-κB Signaling Pathway to Alleviate Inflammatory Response in Rats with Knee Osteoarthritis
摘要
Abstract
Objective:To investigate the effect of geniposide on knee osteoarthritis(KOA)in rats and its potential mechanisms.Methods:A rat KOA model was established using sodium iodoacetate,and the rats were randomly divided into a normal control group,a model control group,geniposide groups(30 mg/kg,60 mg/kg,and 120 mg/kg),and a diclofenac group(6 mg/kg,positive control).Pathological changes in carti-lage tissue were observed using hematoxylin and eosin(HE)and safranin O-fast green(SO/FG)staining,with quantitative scoring performed using the Mankin scoring system.Transmission electron microscopy(TEM)was utilized to observe the ultrastructure of cartilage tissue.Ser-um levels of matrix metalloproteinase-13(MMP-13),interleukin-1β(IL-1β),IL-6,tumor necrosis factor-α(TNF-α),malondialdehyde(MDA),superoxide dismutase(SOD),glutathione peroxidase(GPx),and catalase(CAT)were detected using ELISA kits.The mRNA ex-pression levels of Toll-like receptor 4(Tlr4),myeloid differentiation factor 88(Myd88),and nuclear factor kappa-B(Nf-κb)were measured using quantitative reverse transcription PCR(RT-qPCR).Protein expressions related to the TLR4/MyD88/NF-κB pathway were assessed u-sing Western blot analysis.Results:Compared with the normal control group,the model control group exhibited significant cartilage destruc-tion,joint inflammation,and oxidative stress,with markedly increased protein and mRNA expression of TLR4,MyD88,and NF-κB(P<0.01).In the geniposide groups(60 mg/kg and 120 mg/kg),cartilage damage and lesions were significantly improved compared with those in the model control group.Serum levels of MMP-13,IL-1β,TNF-α,and IL-6 were significantly reduced(P<0.05 or P<0.01),and the oxidative stress response was significantly inhibited.The protein and mRNA expression of TLR4,MyD88,and NF-κB were significantly downregulated(P<0.05 or P<0.01).Conclusion:Geniposide reduced the release of inflammatory cytokines and oxidative stress levels by regulating the TLR4/MyD88/NF-κB signaling pathway,thereby protecting articular cartilage from injury in KOA rats.关键词
栀子苷/膝骨关节炎/软骨损伤/氧化应激/炎症反应/Toll样受体4/髓样分化因子88/核转录因子κBKey words
Geniposide/Knee osteoarthritis/Cartilage injury/Oxidative stress/Inflammatory response/Toll-like receptor 4/myeloid differenti-ation factor 88/Nuclear factor kappa-B引用本文复制引用
张健,颜运涛,王响,焦永伟,李锡,杨琦,任伟亮..栀子苷调节TLR4/MyD88/NF-κB信号通路缓解膝骨关节炎大鼠的炎症反应[J].中药药理与临床,2025,41(5):22-27,6.基金项目
河北省重点研发计划项目(编号:223777125D) (编号:223777125D)
河北省中医药管理局科研计划项目(编号:2024005). (编号:2024005)