款冬花熏吸干预香烟诱导小鼠肺损伤的代谢组学研究

Effect of fumigation therapy of Flos Farfarae in cigarette smoke-induced lung injury mice based on metabolomics

本研究旨在探讨款冬花熏吸疗法对香烟烟雾诱导的肺损伤模型小鼠的改善作用,并分析其对肺损伤小鼠肺组织代谢轮廓的影响。所有动物福利和实验过程均遵循山西大学动物伦理委员会的规定(批准号:SXULL2019014)。通过HS-GC-MS分析鉴定款冬花热挥发性成分23种。款冬花熏吸干预能够改善香烟烟雾诱导的肺损伤模型小鼠的肺组织形态,降低白介素-6(interleukin-6,IL-6)和白介素-1β(interleukin-1β,IL-1β)的水平。采集各组小鼠的肺组织进行基于UHPLC-QTOF MS的代谢组学分析,结果显示香烟暴露后肺组织中有70个代谢物水平显著变化,经款冬花熏吸干预后能回调溶血磷脂酰胆碱(lysophosphatidylcholine,LPC)、12-HETE、腺苷、黄嘌呤等35个差异代谢物水平。LPC、12-HETE、腺苷、黄嘌呤等代谢物与体内的炎症反应密切相关,这些回调的代谢物集中在嘌呤代谢、花生四烯酸代谢、磷脂代谢和丙酮酸代谢通路上。说明款冬花挥发性成分中含有的萜类物质可能通过调节肺组织中溶血磷脂酰胆碱、12-HETE、腺苷等炎性反应相关代谢物的水平,进而通过嘌呤代谢、磷脂代谢等途径缓解香烟烟雾诱导小鼠肺部炎症。本研究证明了款冬花传统熏吸应用的科学内涵,为款冬花熏吸应用及产品开发提供了理论依据。

This study aimed to investigate the effect of Flos Farfarae(FF)fumigation on cigarette smokeinduced lung injury mice,and analyze the metabolic profile of lung tissue by metabolomics.All animal experiments were conducted under the guidance and approval of the Animal Ethics Review Committee of Shanxi University(Approval number:SXULL2019014).By using HS-GC-MS to analyze volatile components of Flos Farfarae,23 compounds were identified.The results showed that FF fumigation improved the lung tissue morphology of cigarette smoke-induced lung injury mice,lowered the levels of interleukin 6(IL-6)and interleukin-1β(IL-1β).The lung tissue samples were applied for metabolomic analysis based on UHPLC-QTOF MS,the results showed that 70 metabolites were changed in the lung tissue of mice after cigarette exposure,and 35 of them could be regulated,including lysophosphatidylcholine(LPC),12-HETE,adenosine,and xanthine.These metabolites,such as LPC,12-HETE,adenosine,and xanthine were mainly associated with the body's inflammatory response.It was observed that these metabolites are primarily involved in purine metabolism,arachidonic acid metabolism,phospholipid metabolism,and pyruvate metabolism pathways.These findings suggest that the volatile terpenoids in the FF may regulate the metabolites associated with the inflammatory response in the lung tissue,such as lysophosphatidylcholine,12-HETE,and adenosine,which could further alleviate lung inflammation induced by cigarette smoke through the metabolic pathways of purine metabolism and others.This study proved the scientific basis of the traditional application of FF fumigation,and provided a theoretical basis for the further product development.