| 引用本文: |
张钧岚, 赵芳, 张也, 戴宗顺, 林也, 蔡雄, 唐媛媛.基于代谢组学联合分析的青附蠲痹汤调控精氨酸代谢治疗类风湿关节炎病证的机制研究[J].湖南中医药大学学报,2026,46(4):697-706[点击复制] |
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| 基于代谢组学联合分析的青附蠲痹汤调控精氨酸代谢治疗类风湿关节炎病证的机制研究 |
| 张钧岚,赵芳,张也,戴宗顺,林也,蔡雄,唐媛媛 |
| (湖南中医药大学中医药科学院, 湖南 长沙 410208;湖南中医药大学针灸推拿与康复学院, 湖南 长沙 410208;宁乡市人民医院中医风湿免疫科, 湖南 长沙 410600) |
| 摘要: |
| 目的 基于代谢组学与网络药理学联合分析，探讨青附蠲痹汤（QFJBT）治疗佐剂性关节炎（AIA）风寒湿痹证大鼠的作用机制，并重点验证其对精氨酸代谢通路的调控作用。方法 将48只SPF级雄性SD大鼠随机分为空白对照组（8只）与造模组（40只），前者注射等体积生理盐水，后者用于建立AIA风寒湿痹证大鼠模型。造模结束后次日，将造模成功的大鼠随机均分为模型组、甲氨蝶呤（MTX）组及QFJBT低、中、高剂量组，每组8只。给药干预期间，空白对照组与模型组每日灌胃等体积生理盐水，1次/天；QFJBT低、中、高剂量组分别按4.59、9.18、18.36 g/kg剂量灌胃给药，1次/d;MTX组按1 mg/kg剂量灌胃甲氨蝶呤，每3天1次。各组均连续干预42 d，采用超高效液相色谱-四极杆-飞行时间质谱联用仪非靶向代谢组学技术分析大鼠血浆代谢谱，通过多元统计分析筛选差异代谢物及关键信号通路；结合网络药理学筛选交集靶点，并利用Metscape构建“化合物-反应-酶-基因”通路，对核心通路进行整合分析；采用Western blot对关键靶点进行验证。结果 QFJBT可显著改善AIA大鼠异常代谢状态,精氨酸生物合成被鉴定为关键代谢途径。整合分析提示，精氨酸代谢通路（涵盖精氨酸的合成、分解及功能调控）可能是QFJBT发挥作用的核心代谢基础。Western blot结果显示，QFJBT可下调精氨酸酶1/2(Arginase 1/2)(P<0.001)和诱导型一氧化氮合酶（i NOS）表达水平（P<0.05），并促进精氨基琥珀酸合成酶1(ASS1)表达恢复（P<0.05）；同时可抑制mTOR(P<0.05)及NF-κB信号通路的过度活化（P<0.001）。结论 QFJBT可能通过协同抑制mTOR/NF-κB信号轴，调控精氨酸代谢通路，从代谢、免疫、炎症及氧化应激等多个层面发挥综合调节作用。 |
| 关键词: 类风湿关节炎|青附蠲痹汤|佐剂性关节炎|风寒湿痹证|代谢组学|精氨酸代谢 |
| DOI：10.3969/j.issn.1674-070X.2026.04.006 |
| 投稿时间：2025-12-29 |
| 基金项目:国家自然科学基金面上项目(82405235);湖南省自然科学基金项目(2023JJ40477);长沙市自然科学基金项目(kq2208499);湖南中医药大学院校联合课题重点项目(2022XYLH158) |
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| Mechanism of Qingfu Juanbi Decoction in regulating arginine metabolism for treating rheumatoid arthritis based on combined metabolomics analysis |
| ZHANG Junlan, ZHAO Fang, ZHANG Ye, DAI Zongshun, LIN Ye, CAI Xiong, TANG Yuanyuan |
| (Institute of Chinese Medical Sciences, Hunan University of Chinese Medicine, Changsha, Hunan 410208, China;School of Acupuncture-moxibustion, Tuina and Rehabilitation, Hunan University of Chinese Medicine, Changsha, Hunan 410208, China;Department of Chinese Medicine Rheumatology, Ningxiang People's Hospital, Changsha, Hunan 410600, China) |
| Abstract: |
| Objective To investigate the mechanisms of Qingfu Juanbi Decoction(QFJBT) in treating adjuvant-induced arthritis(AIA) rats with wind-cold-dampness impediment pattern based on integrated metabolomics and network pharmacology analysis,with a focus on verifying its regulatory effect on the arginine metabolism pathway. Methods Forty-eight SPF male SD rats were randomly divided into a blank control group(n=8) and a modeling group(n=40). The blank control group received an equal volume of normal saline, while the modeling group was used to establish the AIA rat model with wind-cold-dampness impediment pattern.On the day after successful modeling, the model rats were randomly and equally divided into model group, methotrexate(MTX)group, and low-, medium-, and high-dose QFJBT groups, with 8 rats in each group. During the intervention period, the blank control and model groups received an equal volume of normal saline by gavage once daily. The low-, medium-, and high-dose QFJBT groups received QFJBT at doses of 4.59, 9.18, and 18.36 g/kg, respectively, once daily by gavage. The MTX group received methotrexate at 1 mg/kg by gavage once every three days. All groups were continuously treated for 42 days. Rat plasma metabolic profiles were analyzed using untargeted metabolomics based on UPLC-Q-TOF/MS. Multivariate statistical analysis was performed to screen for differential metabolites and key signaling pathways. Combined with network pharmacology, intersecting targets were identified. The Metscape was used to construct a "compound-reaction-enzyme-gene" network, followed by integrative analysis of the core pathways. Key targets were further validated by Western blot. Results QFJBT significantly ameliorated the abnormal metabolic status in AIA rats, and arginine biosynthesis was identified as the key metabolic pathway. Integrative analysis suggested that the arginine metabolic pathway, encompassing arginine synthesis, breakdown, and functional regulation, may represent the core metabolic basis underlying the therapeutic effects of QFJBT. Western blot results demonstrated that QFJBT downregulated the expression of arginase 1/2(P<0.001) and inducible nitric oxide synthase(i NOS)(P<0.05), while promoting the restoration of argininosuccinate synthase 1(ASS1) expression(P<0.05). Additionally, QFJBT inhibited the overactivation of the m TOR(P<0.05) and NF-κB signaling pathways(P<0.001). Conclusion QFJBT may exert its comprehensive regulatory effects across multiple levels including metabolism, immunity, inflammation, and oxidative stress by synergistically inhibiting the mTOR/NF-κB signaling axis and thereby modulating the arginine metabolic pathway. |
| Key words: rheumatoid arthritis|Qingfu Juanbi Decoction|adjuvant-induced arthritis|wind-cold-dampness impediment pattern|metabolomics|arginine metabolism |
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