中药新药与临床药理2026，Vol.37Issue(6)：1017-1027,11.DOI:10.19378/j.issn.1003-9783.2026.06.004
基于 PI3K/Akt/mTOR信号通路探讨土家药铃铃菜干预类风湿关节炎的机制
Investigating the Mechanism of the Tujia Herbal Medicine Linglingcai in Rheumatoid Arthritis Intervention Based on the PI3K/Akt/mTOR Signaling Pathway
摘要
Abstract
Objective To investigate the pharmacodynamic mechanism of the Tujia herbal medicine Linglingcai(LLC)in the intervention of rheumatoid arthritis(RA)from the perspective of the PI3K/Akt/mTOR signaling pathway.Methods A total of 36 male SD rats were randomly divided into six groups:normal control,model control,tripterygium glycosides(10 mg·kg-1),and LLC low-(15 mg·kg-1),medium-(30 mg·kg-1),and high-dose(60 mg·kg-1)groups.Except for the normal control group,a rat model of collagen-induced arthritis(CIA)was established by subcutaneous injection of bovine type Ⅱ collagen in all other groups.After successful modeling,the rats were administered the respective treatments by gavage for five consecutive weeks.Pathological changes in the rat ankle joint tissues were assessed using HE staining.Serum levels of interleukin-1β(IL-1β),interleukin-6(IL-6),and tumor necrosis factor-alpha(TNF-α)were measured using ELISA kits.The relative mRNA expression levels of IL-1β,IL-6,and TNF-α in rat serum were determined by RT-PCR.The major chemical components of LLC were identified using untargeted metabolomics(TIC).Network pharmacology was employed to predict the potential mechanisms by which LLC intervenes in RA.Subsequently,animal experiments were conducted to validate the mechanism of the signaling pathway predicted by network pharmacology.Results Compared with the model group,the joint swelling scores and gait scores of rats in the tripterygium glycosides group and all LLC dose groups were significantly reduced(P＜0.01,P＜0.05).Histopathological examination showed amelioration of inflammatory cell infiltration.Serum levels and mRNA expression of IL-1β,IL-6,and TNF-α were significantly decreased(P＜0.01,P＜0.05).Untargeted metabolomics identified a total of 2 372 chemical components in LLC.Network pharmacology results indicated that the PI3K/Akt/mTOR signaling pathway might be the primary pathway through which LLC intervenes in RA,with PI3K,Akt,and mTOR identified as potential key targets.Immunohistochemistry(IHC)results demonstrated that LLC inhibited the phosphorylation activity of the PI3K/Akt/mTOR pathway in rat ankle joint cells.Conclusion LLC may exert its anti-rheumatoid arthritis effects by inhibiting the phosphorylation of the PI3K/Akt/mTOR signaling pathway,thereby reducing the infiltration of inflammatory cells into the joints.关键词
铃铃菜/土家药/类风湿关节炎/网络药理学/PI3K/Akt/mTOR信号通路/大鼠Key words
Linglingcai/Tujia herbal medicine/rheumatoid arthritis/network pharmacology/PI3K/Akt/mTOR signaling pathway/rats分类
医药卫生引用本文复制引用
王怡然,韩文轩,杨文婧,刘浩然,吴昊,董倩男..基于 PI3K/Akt/mTOR信号通路探讨土家药铃铃菜干预类风湿关节炎的机制[J].中药新药与临床药理,2026,37(6):1017-1027,11.基金项目
国家自然科学基金资助项目(81960776) （81960776）
恩施州科技计划青年人才类项目(D20220034) （D20220034）
湖北恩施学校级科研项目(KYJZ202307). （KYJZ202307）
