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基于代谢组学研究经典名方达原饮对RSV寒湿郁肺证小鼠模型的作用机制

Mechanism of Famous Classical Formula Dayuanyin Decoction(达原饮)in Treatment of Mice Model with RSV and Cold-Dampness in Lung Syndrome Based on Metabonomics
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摘要 目的 基于超高液相色谱-四极杆静电场轨道阱质谱法(ultra-high performance liquid chromatography-quadrupole electrostatic field orbital trap mass spectrometry, UHPLC-QE-MS)研究达原饮对模型小鼠的干预及肺组织代谢物的影响,以探究达原饮治疗呼吸道合胞病毒(Respiratory syncytial virus, RSV)寒湿郁肺证的作用机制。方法 采用寒湿刺激加RSV滴鼻感染的方法建立RSV寒湿郁肺证小鼠模型,综合小鼠活动状态、肺指数和肺组织病理,结合肺组织中白介素-6(Interleukin-6,IL-6)和白介素-1β(Interleukin-1β,IL-1β)炎症因子的含量,初步评价达原饮对RSV寒湿郁肺证小鼠的治疗效果。利用UHPLC-QE-MS技术检测正常组、模型组、达原饮中剂量组小鼠肺组织代谢物,以正交偏最小二判别分析进行多元统计分析模式识别,以P<0.05且VIP值>1为条件筛选差异代谢物,并借助MetaboAnalyst 5.0数据库富集代谢通路。结果 达原饮可以显著改善RSV寒湿郁肺证小鼠的一般状态,降低肺指数,改善肺组织病理,并降低肺组织中IL-6、IL-1β的含量。代谢组学结果显示,与达原饮调控相关的差异代谢物共有35个,主要涉及嘌呤代谢、花生四烯酸、甘氨酸、丝氨酸和苏氨酸代谢等代谢通路。结论 从代谢组学角度分析了达原饮治疗RSV寒湿郁肺证的作用机制,为达原饮抗病毒研究及临床应用奠定了基础。 Objective Ultra-high performance liquid chromatography-quadrupole electrostatic field orbital trap mass spectrometry(UHPLC-QE-MS)was employed in this study to observe the effect of Dayuanyin Decoction(达原饮)on the lung tissues metabolites of model mice and reveal the mechanism of Dayuanyin Decoction in the treatment of respiratory syncytial virus(RSV)with cold-dampness in lung syndrome.Methods The mice were placed in a cold-dampness environment and infected with RSV to establish the mouse model.The therapeutic effect of Dayuanyin Decoction on RSV with cold-dampness in lung syndrome was preliminarily evaluated based on the mice activity status,lung index,lung tissue morphology,and the content of inflammatory cytokines such as interleukin-6(IL-6)and interleukin-1β(IL-1β).UHPLC-QE-MS was employed to profile the endogenous metabolites of lung tissues samples in normal group,model group and medium-dose Dayuanyin Decoction group.Orthogonal partial least squares-discriminant analysis(OPLS-DA)was performed for multivariate analyses pattern recognition.Potential biomarkers were screened with P<0.05 and VIP>1,and the metabolic pathways were enriched by MetaboAnalyst 5.0.Results Dayuanyin Decoction significantly improved the general state and lung tissue morphology of mice with RSV and cold-dampness in lung syndrome,reduced the lung index and lowered the levels of IL-6 and IL-1βin lung.A total of 35 potential biomarkers were predicted to be related to the regulatory effect of Dayuanyin Decoction,which were mainly involved in purine me-tabolism,arachidonic acid metabolism,glycine,serine and threonine metabolism.Conclusion This study employed metabolomics to analyze the mechanism of Dayuanyin Decoction in the treatment of RSV with cold-dampness in lung syndrome,forming a foundation for the antiviral research and clinical application of Dayuanyin Decoction.
作者 张茹 王晓雪 杜海涛 祁婉莹 王仪 丁晓彦 周倩 刘善新 龚彦胜 王平 ZHANG Ru;WANG Xiaoxue;DU Haitao;QI Wanying;WANG Yi;DING Xiaoyan;ZHOU Qian;LIU Shanxin;GONG Yansheng;WANG Ping(Shandong University of Traditional Chinese Medicine,Jinan 250355,Shandong,China;Shandong Academy of Chinese Medicine,Jinan 250014,Shandong,China;State Key Laboratory of Precision Measurement Technology and Instruments,Tianjin University,Tianjin 300072,China;Affiliated Hospital of Shandong Academy of Traditional Chinese Medicine,Jinan 250014,Shandong,China)
出处 《中华中医药学刊》 CAS 北大核心 2024年第3期99-103,I0006-I0009,共9页 Chinese Archives of Traditional Chinese Medicine
基金 国家重点研发计划政府间国际科技创新合作项目(2019YFE0117800) 山东省重大科技创新工程项目(2020CXGC010505-04) 山东省新旧动能转换重大工程重大课题攻关项目(202006) 济南市“新高校20条”项目(202228121)。
关键词 达原饮 呼吸道合胞病毒 代谢组学 寒湿郁肺 Dayuanyin Decoction(达原饮) respiratory syncytial virus metabonomics cold-dampness in lung syndrome
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