牛旁子治疗小鼠病毒性肺炎后肺纤维化的机制：基于代谢组学、网络药理学和实验验证方法

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Abstract：ObjectiveToexplorethetherapeuticmechanismofArctiumlappaextractfortreatmentofPost-ViralPneumonia PulmonaryFibrosis （PPF）.Methods Thechemicalconstituentsof Arctiumlappaextractswere identifiedusing UHPLC-Q-TOFMS/MS.Mouse models of pulmonary fibrosis established by tracheal instilltion of bleomycin were treated with Arctiumlappa extract，and body weightchanges were recorded andlung tisue pathology was examinedusingHEand Mason staining. Metabolomicsanalysiswasusedtoidentifythediferentialmetabolitesandtheassociatedmetabolicpathwaysinthetreated mice.Thecommon targetsofviral pneumoniaand pulmonary fibrosis wereacquiredfrom thepubliclyavailable databases， andthecore targetsandactiveconstituentswere screened using the protein-protein interaction （PPI） network，GOand KEGG enrichmentanalyses，andmoleculardocking，anda"gene-metabolite"regulatorynetworkwasconstructed.Theexprsionsof thecoretargetsweredetectedinthelungtisuesofthetreatedmiceusingWesternbloting.ResultsFifty-threechemical constituents wereidentifiedfromArctium lappa extract.Inthemousemodelsof pulmonaryfibrosis，treatmentwithArctium lappaextractsignificantlyimprovedweightlossandamelioratedlunginflammationandfibrosis.Thedierentialmetabolites inthe treated mice wereenriched inenergy metabolismpathways involving citratecycle，pentosephosphatepathway glycolysis，tryptophan metabolism，glutamate metabolism and glutathione metabolism，which regulatedthe productionof energy metabolismintermediates.Twenty-threkeyactivecompounds （mostlylignansand phenolicacids）and82coretargets were screned，which wereasociated withthenon-canonical Smadsignalingpathways （includingPI3K/AKT，HF-1，MAPK， andFoxo）thatparticipated intheregulationofenergymetabolism.Arctiumlappextractalsoregulatedtheexpresionsof epithelial-mesenchymaltransition（EM）relatedproteins（fibronectinvimentimandSnail，tc.）andinibitedMAPK signalingpathwayactivation.Conclusion PreliminaryfindingssuggestthatArctium lappatreatsfibrosisbyregulating metabolism toinhibitEMTandinvolvesthe modulationof non-canonicalSmad signalingpathways，suchas MAPKproviding theoretical support for its clinical application and further research in treating PPF.

Keywords： Arctium lappa; post-viral pneumonia pulmonary fibrosis; network pharmacology; metabolomics; MAPK

病毒性肺炎是由病毒感染肺实质引起的肺部炎症，病毒通过直接损伤或持续的免疫反应引起肺损伤，肺损伤后的异常修复可导致肺纤维化（PF）2]。（剩余23384字）