时珍国医国药2026，Vol.37Issue(11)：2007-2014,8.DOI:10.70976/j.1008-0805.SZGYGY-2026-1102
金芪志颗粒调控ATF-4/NUPR1信号轴抑制软骨细胞铁死亡改善膝骨关节炎的机制
Study on the mechanism of Jinqizhi Granule(金芪志颗粒)in regulating the ATF-4/NUPR1 signaling pathway to inhibit ferroptosis in chondrocytes and alleviate knee osteoarthritis
摘要
Abstract
Objective To investigate whether Jinqizhi Granule(金芪志颗粒,JQZG)can inhibit chondrocyte ferroptosis by modulating the ATF-4/NUPR1 signaling pathway in knee osteoarthritis(KOA)rats,thereby protecting cartilage tissue.Methods A KOA rat model was established via meniscal instability surgery.Rats were divided into five groups:control,KOA,and low/medium/high-dose JQZG groups(n=8 per group).The control group underwent sham operation.Two weeks post-operation,low/medium/high-dose groups received oral administration of JQZG at 6.4,12.8,and 25.6 g/(kg·d),respectively.The sham-operated and KOA groups received saline via oral gavage once daily for 4 consecutive weeks.Chondral tissue pathological changes were observed using Fuchsin-Green staining and scored according to the Mankin grading system.Western blot(WB)and qPCR were used to detect chondral tissue markers of the ATF-4/NUPR1 pathway[Activated Transcription Factor 4(ATF-4),Nucleoprotein 1(NUPR1)],ferroptosis markers[acyl-CoA synthase 4(ACSL4),glutathione peroxidase 4(GPX4),solute carrier family 7 member 11(SLC7A11)],and matrix metabolism mark-ers[matrix metalloproteinase-13(MMP-13),type II collagen(Collagen II)].Immunohistochemistry(IHC)examined the expression levels of ATF-4,NUPR1,ACSL4,GPX4,and SLC7A11 in cartilage tissue across all groups.Results Compared with the sham-operated group,rats in the KOA group exhibited severe cartilage margin destruction,elevated Mankin scores,and decreased protein and mRNA expression levels of GPX4,SLC7A11,and Collagen II,while showing increased expression levels of ATF-4,NUPR1,ACSL4,and MMP-13(P<0.01).Compared with the KOA group,all intervention groups exhibited decreased ATF-4,NUPR1,ACSL4,and MMP-13 protein and mRNA expression levels(P<0.01),while GPX4,SLC7A11,and Collagen II protein and mRNA expression levels were increased.IHC analysis of cartilage tissue after intervention showed a significant decrease in ATF-4,NUPR1,ACSL4 in cartilage tissue was significantly reduced,while the proportion of GPX4 and SLC7A11 positive areas was markedly increased.Conclusion JQZG can improve cartilage damage in KOA by regulating the ATF-4/NUPR1 pathway to inhibit ferroptosis in chondrocytes.关键词
金芪志颗粒/膝骨关节炎/软骨退变/铁死亡/ATF-4/NUPR1信号轴Key words
Jinqizhi Granule(金芪志颗粒)/Knee osteoarthritis/Cartilage degeneration/Ferroptosis/ATF-4/NUPR1 Signal-ing pathway分类
医药卫生引用本文复制引用
匡辰,魏义保,刘德仁,胡恩睿,龚子健,茆军,张农山,廖太阳,王培民..金芪志颗粒调控ATF-4/NUPR1信号轴抑制软骨细胞铁死亡改善膝骨关节炎的机制[J].时珍国医国药,2026,37(11):2007-2014,8.基金项目
国家自然科学基金(82305276) （82305276）
江苏省中医药科技发展项目(QN202105) （QN202105）
江苏省高等学校自然科学研究项目(22KJB360008) （22KJB360008）
江苏省中医院膝关节骨关节炎临床医学创新中心项目(Y2023zx05) （Y2023zx05）
江苏省医学重点学科(实验室)培育单位项目(JSDW202252) （实验室）
苏州市科技发展计划项目(SYSD2020036) （SYSD2020036）
苏州市吴门医派研究专项科研基金(SYWD2025270) （SYWD2025270）
