南京中医药大学学报2026，Vol.42Issue(8)：1185-1193,9.DOI:10.14148/j.issn.1672-0482.2026.1185
基于Nrf2/HO-1信号通路探讨异甘草素改善KOA痛敏的机制研究
Research on the Mechanism of Isoliquiritigenin Improving Pain Sensitivity in KOA Based on the Nrf2/HO-1 Signaling Pathway
摘要
Abstract
OBJECTIVE To investigate the mechanism by which isoliquiritigenin(ISL)improves pain hypersensitivity in knee osteoarthritis(KOA)by regulating the Nrf2/HO-1 signaling pathway.METHODS Fifty C57BL/6J mice were randomly divided into five groups(n=10):control group,KOA group,low-dose ISL group(10 mg·kg-1),high-dose ISL group(40 mg·kg-1),and celecoxib group(43.3 mg·kg-1).A KOA model was established using the destabilization of the medial meniscus(DMM)surgery,and pain hyper-sensitivity was assessed.In vivo experiments included ELISA to measure serum levels of TNF-α,IL-1β,and IL-6;immunofluores-cence to observe TRPA1,TRPV1,and TRPM8 ion channel fluorescence intensity in dorsal root ganglia(DRG);and Western blot to quantify Nrf2,HO-1,PGP9.5,NGF,and Substance P protein expression in DRG.For in vitro experiments,ML385 was used to inhibit the Nrf2/HO-1 pathway,and the effects of ISL on neurons were evaluated after pathway inhibition.RESULTS Compared with the control group,the KOA group exhibited significantly reduced cold and mechanical stimulation thresholds(P<0.01),increased TRPA1,TRPV1,and TRPM8 fluorescence intensity(P<0.01),elevated serum TNF-α,IL-1β,and IL-6 levels(P<0.01),decreased Nrf2 and HO-1 expression,and increased PGP9.5,NGF,and Substance P expression(P<0.01).Compared with the KOA group,both ISL dose groups and the celecoxib group showed significantly improved cold and mechanical stimulation thresholds(P<0.01),reduced TRP channel fluorescence intensity(P<0.01),decreased inflammatory cytokine levels(P<0.05,P<0.01),upregulated Nrf2 and HO-1 expression,and downregulated PGP9.5,NGF,and Substance P expression(P<0.05,P<0.01).In vitro experiments revealed that LPS treatment reduced Nrf2/HO-1 levels(P<0.01),increased PGP9.5,NGF,and Substance P expression(P<0.01),and elevated reactive oxygen species(ROS)(P<0.01).ISL reversed these effects(P<0.01),while ML385 co-treatment abolished ISL's benefits,reactivating ROS and pain-related proteins(P<0.01).CONCLUSION Isoliquiritigenin alleviates KOA pain hypersensitivity by activating the Nrf2/HO-1 signaling pathway.关键词
膝骨关节炎/异甘草素/Nrf2/HO-1信号通路/背根神经节/痛敏Key words
knee osteoarthritis/isoliquiritigenin/Nrf2/HO-1 signaling pathway/dorsal root ganglion/pain sensitivity分类
医药卫生引用本文复制引用
伏厚宇,揭立士,刘江宇,陈颖琦,殷松江,王培民,李晓辰..基于Nrf2/HO-1信号通路探讨异甘草素改善KOA痛敏的机制研究[J].南京中医药大学学报,2026,42(8):1185-1193,9.基金项目
国家自然科学基金青年科学基金项目(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）
江苏省中医院高峰学术人才项目(y2021rc48) （y2021rc48）
江苏省中医院膝关节骨关节炎临床医学创新中心(Y2023zx05) （Y2023zx05）
江苏省医学重点学科(实验室)培育单位(JSDW202252) （实验室）
江苏省高等学校大学生创新创业训练计划(202410315091Y) （202410315091Y）
