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卢一帆, 卢承印, 段峻杰, 熊辉, 陆小龙, 李前, 齐新宇, 伍搏宇, 吴成亮, 苏文杰, 杨卓, 段建辉.基于网络药理学和代谢组学探讨独活寄生汤治疗膝骨关节炎的作用机制[J].湖南中医药大学学报英文版,2025,45(10):1839-1851.[Click to copy
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| 基于网络药理学和代谢组学探讨独活寄生汤治疗膝骨关节炎的作用机制 |
| 卢一帆,卢承印,段峻杰,熊辉,陆小龙,李前,齐新宇,伍搏宇,吴成亮,苏文杰,杨卓,段建辉 |
| (湖南中医药大学附属常德医院, 湖南 常德 415000;湖南中医药大学, 湖南 长沙 410208;河南省洛阳正骨医院/河南省骨科医院, 河南 郑州 450000;湖南中医药大学第一附属医院, 湖南 长沙 410007;广州中医药大学附属东莞医院, 广东 东莞 523000) |
| 摘要: |
| 目的 通过网络药理学和代谢组学探讨独活寄生汤（DHJSD）在治疗膝骨关节炎（KOA）中的作用机制。方法 共纳入40只SD大鼠，随机分空白组、模型组、DHJSD组和盐酸氨基葡萄糖（GH）组，每组10只。除空白组外，其余各组均建立KOA模型，造模方法为关节腔内注射40 mg/mL的碘乙酸单钠50 μL。DHJSD组予以灌胃DHJSD（9.56 g/kg），GH组予以GH溶液（1 g/kg），模型组和空白组予以等体积生理盐水，连续灌胃7 d。采用液相色谱-串联质谱技术检测DHJSD在大鼠血清中的成分，利用网络药理学分析挖掘DHJSD治疗KOA的潜在关键靶点。在建立KOA大鼠模型后，通过HE染色、RT-qPCR及Western blot技术验证DHJSD对KOA中的核因子-κB（NF-κB）、磷脂酰肌醇3激酶/哺乳动物雷帕霉素靶蛋白（PI3K/mTOR）信号通路的调控作用，并利用代谢组学方法筛选差异代谢物。结果 共鉴定出49种成分，主要包括黄酮类、萜类、苯丙素类和生物碱类成分。网络药理学和代谢组学分析显示，Toll样受体信号通路、肿瘤坏死因子信号通路、白细胞介素17和鞘脂代谢信号通路可能是DHJSD治疗KOA的重要作用靶点。动物实验结果表明，DHJSD可显著改善KOA模型大鼠的软骨结构，减少纤维化，缓解炎症反应，下调NF-κB p65和p-PI3K的蛋白表达（P＜0.05）。结论 DHJSD在KOA中的作用可能与NF-κB、PI3K/mTOR及鞘脂代谢等信号通路和代谢途径的调节相关，从而实现代谢稳态改善与炎症反应缓解，并促进关节修复。 |
| 关键词: 膝骨关节炎 独活寄生汤 网络药理学 代谢组学 鞘脂代谢 |
| DOI：10.3969/j.issn.1674-070X.2025.10.006 |
| Received:August 07, 2025 |
| 基金项目:湖南省自然科学基金项目（2022JJ30087，2024JJ5002）；常德市科技研发与科技创新指导性项目（CDKJJ20220357）；湖南省自然科学基金地区联合基金项目（2025JJ70653）；湖南中医药大学本科生科研创新基金项目（2023BKS023）；湖南中医药大学校级科研项目（2022XYLH045，2022XYLH051）。 |
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| Mechanism of action of Duhuo Jisheng Decoction in treating knee osteoarthritis based on network pharmacology and metabolomics |
| LU Yifan, LU Chengyin, DUAN Junjie, XIONG Hui, LU Xiaolong, LI Qian, QI Xinyu, WU Boyu, WU Chengliang, SU Wenjie, YANG Zhuo, DUAN Jianhui |
| (Changde Hospital of Hunan University of Chinese Medicine, Changde, Hunan 415000, China;Hunan University of Chinese Medicine, Changsha, Hunan 410208, China;Luoyang Orthopedic-Traumotological Hospital of Henan Province/Henan Provincial Orthopedic Hospital, Zhengzhou, Henan 450000, China;The First Hospital of Hunan University of Chinese Medicine, Changsha, Hunan 410007, China;Dongguan Hospital of Guangzhou University of Chinese Medicine, Dongguan, Guangdong 523000, China) |
| Abstract: |
| Objective To explore the mechanism of action of Duhuo Jisheng Decoction (DHJSD) in the treatment of knee osteoarthritis (KOA) through network pharmacology and metabolomics. Methods A total of 40 SD rats were randomly divided into a blank group, a model group, a DHJSD group, and a glucosamine hydrochloride (GH) group, with 10 rats in each group. Except the blank group, KOA models were established in all the other groups by intra-articular injection of 50 μL of sodium iodoacetate (40 mg/mL). The DHJSD group was administered DHJSD (9.56 g/kg) via gavage, the GH group was given glucosamine hydrochloride (1 g/kg), while the model and blank groups received an equal volume of normal saline. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to check the serum components of DHJSD, and network pharmacology analysis to identify potential key targets of DHJSD in the treatment of KOA. After establishing the KOA rat model, HE staining, RT-qPCR, and Western blot were performed to verify the regulatory effects of DHJSD on the nuclear factor kappa-B (NF-κB) and phosphoinositide 3-kinase/mammalian target of rapamycin (PI3K/mTOR) signaling pathways in KOA. Additionally, metabolomics was employed to screen differential metabolites. Results A total of 49 components were identified, primarily including flavonoids, terpenoids, phenylpropanoids, and alkaloids. Network pharmacology and metabolomics analyses revealed that the signaling pathways of Toll-like receptor, tumor necrosis factor (TNF), interleukin-17 (IL-17), and sphingolipid metabolism may represent key therapeutic targets of DHJSD in the treatment of KOA. Animal experiments demonstrated that DHJSD significantly improved the cartilage structure in KOA model rats, reduced fibrosis, alleviated inflammatory responses, and downregulated the protein expression of NF-κB p65 and p-PI3K (P＜0.05). Conclusion The therapeutic effects of DHJSD in KOA treatment may be related to the regulation of signaling pathways and metabolic pathways such as NF-κB, PI3K/mTOR, and sphingolipid metabolism, thereby achieving the improvement of metabolic homeostasis, the alleviation of inflammatory responses, and the promotion of joint repair. |
| Key words: knee osteoarthritis Duhuo Jisheng Decoction network pharmacology metabolomics sphingolipid metabolism |
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