中国实验方剂学杂志2026，Vol.32Issue(17)：46-58,13.DOI:10.13422/j.cnki.syfjx.20260718
甘草附子汤调控PI3K/Akt/mTOR信号通路促进自噬改善大鼠膝骨关节炎的机制
Mechanism of Gancao Fuzitang Improving Knee Osteoarthritis in Rats via Regulating PI3K/Akt/mTOR Signaling Pathway and Promoting Autophagy
摘要
Abstract
Objective:This paper aims to investigate the intervention effect and molecular mechanism of Gancao Fuzitang(GCFZT)in knee osteoarthritis(KOA).Methods:Network pharmacology was employed to predict the key targets and signaling pathways of GCFZT.Fifty SD rats were randomly divided into a sham group,a model group(KOA),a low-dose GCFZT group(GCFZT-L,2.8 g·kg-1),a high-dose GCFZT group(GCFZT-H,5.6 g·kg-1),and a positive drug celecoxib group(Celecoxib,20 mg·kg-1),with 10 rats in each group.The rats in the sham group and the model group were given an equal volume of distilled water.Except for the sham group,the other four groups underwent anterior cruciate ligament transection to establish the KOA rat model.After successful modeling,the rats in each group received intragastric administration once a day for eight consecutive weeks.The structural changes of cartilage and subchondral bone were assessed via micro-computed tomography(micro-CT)and histological staining.The levels of inflammatory factors in the serum,such as interleukin-1β(IL-1β),IL-6,and tumor necrosis factor-α(TNF-α)were measured using an enzyme linked immunosorbent assay(ELISA)kit.Real-time quantitative polymerase chain reaction(Real-time PCR),Western blot,and immunohistochemistry were used to detect changes in the expression of autophagy-related proteins such as microtubule-associated protein 1 light chain 3B(LC3B),selective autophagy junction protein 62(p62),and autophagy key molecule yeast Atg6 homolog(Beclin-1)in articular cartilage,as well as key molecules of the phosphatidylinositol 3 kinase(PI3K)/protein kinase B(Akt)/mammalian target of rapamycin(mTOR)signaling pathway.Results:Network pharmacology analysis suggests that GCFZT may exert anti-osteoarthritic effects through regulating the PI3K/Akt/mTOR pathway.In vivo experiment shows that GCFZT can significantly improve cartilage degeneration and attenuate subchondral bone destruction in KOA rats.Detection results of inflammatory factors in the serum reveal that,compared with those in the sham group,the levels of IL-6,IL-1β,and TNF-α in the serum of rats in the KOA group are significantly increased(P<0.05).Compared with those in the KOA group,the levels of these three inflammatory factors in the GCFZT-L,GCFZT-H,and Celecoxib groups were significantly decreased(P<0.05).However,there was no statistically significant difference in these three inflammatory factor levels between the GCFZT-H group and the celecoxib group.These findings suggest that GCFZT can effectively inhibit the systemic inflammatory response in KOA rats.Mechanism research indicates that GCFZT inhibits activation of the PI3K/Akt/mTOR pathway,thereby enhancing autophagic activity and improving chondrocyte function and matrix degeneration.Conclusion:GCFZT improves cartilage and subchondral bone damage in KOA rats by inhibiting the PI3K/Akt/mTOR signaling pathway and promoting autophagy.These findings provide theoretical evidence for the application of GCFZT in the prevention and treatment of osteoarthritis.关键词
甘草附子汤/膝骨关节炎/磷脂酰肌醇3-激酶(PI3K)/蛋白激酶B(Akt)/哺乳动物雷帕霉素靶蛋白(mTOR)/自噬/炎症Key words
Gancao Fuzitang/knee osteoarthritis/phosphatidylinositol 3 kinase(PI3K)/protein kinase B(Akt)/mammalian target of rapamycin(mTOR)/autophagy/inflammation分类
医药卫生引用本文复制引用
王小超,刘满格,肖嘉聪,李泽晖,郭达,蔡育霖,字淳坚,曹学伟..甘草附子汤调控PI3K/Akt/mTOR信号通路促进自噬改善大鼠膝骨关节炎的机制[J].中国实验方剂学杂志,2026,32(17):46-58,13.基金项目
黄宪章广东省名中医传承工作室项目(粤中医办函[2020]1号) （粤中医办函[2020]1号）
广东省基础与应用基础研究基金企业联合基金项目(2022B1515230008) （2022B1515230008）
广州市科技计划项目(2024A03J0118) （2024A03J0118）
