基于网络药理学和分子对接探究黄芩素治疗羊源肺炎克雷伯菌造成肺损伤的作用机制OA

In order to investigate the mechanism of action of baicalein in the treatment of lung injury caused by Klebsiella pneumoniae infection,the study employed network pharmacology techniques,utilizing the STRING protein interaction database to construct a protein-protein interaction(PPI)network.The DAVID database was applied for Gene Ontology(GO)functional and KEGG pathway enrichment analysis.Molecular docking technology assessed the docking capability between the drug and core targets.The minimum inhibitory concentration(MIC)of baicalein against Klebsiella pneumoniae was determined in vitro,with MIC curves plotted and antimicrobial susceptibility testing conducted.Thirty 6-week-old SPF-grade Balb/c mice were divided into control group,model group,low-dose baicalein group(50 mg/kg),medium-dose baicalein group(100 mg/kg),high-dose baicalein group(150 mg/kg),and positive control group(amikacin,200 mg/kg).The control group received no treatment;the remaining five groups were intraperitoneally injected with 0.015 mL/g of Klebsiella pneumoniae suspension.From the second day after injection,each dose group of baicalein was administered baicalein by gavage,and the positive control group was administered amikacin by gavage once daily for one week.Following the conclusion of the experiment,mice were necropsied to observe necropsy lesions and histopathological changes,and to determine the colonization levels of Klebsiella pneumoniae in mouse lung tissue.The concentrations of cytokines including tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),interleukin-1β(IL-1β),and interleukin-10(IL-10)in serum were detected using the ELISA method.The results indicated that network pharmacology techniques identified 17 core targets and 140 signaling pathways.Baicalein exhibited stable molecular docking with core targets including B-cell lymphoma 2(BCL-2),IL-6,nuclear factor κB1(NFκB1),signal transducer and activator of transcription 3(STAT3),TNF-α,and tumor suppressor protein p53(TP53).Combined with KEGG enrichment analysis,baicalein might exert its effects through signaling pathways such as NF-κB,phosphoinositide 3-kinase-protein kinase B,and hypoxia-inducible factor.The minimum inhibitory concentration(MIC)of baicalein against Klebsiella pneumoniae was 2 048 μg/mL,with optimal antibacterial effects observed at this concentration.Compared with the model group,the high-dose baicalein group exhibited more intact lung tissue structure and significantly reduced inflammatory cell infiltration.The colonization of Klebsiella pneumoniae in mouse lungs was significantly decreased(P<0.01),demonstrating pronounced therapeutic efficacy.In the low-dose baicalein group,serum concentrations of TNF-α,IL-6,IL-1β,and IL-10 were significantly decreased(P<0.05).Serum concentrations of TNF-α,IL-6,IL-1β,and IL-10 were significantly decreased in both the medium-and high-dose baicalein groups as well as the positive control group(P<0.01).The results indicated that baicalein exhibited therapeutic effects on lung injury caused by Klebsiella pneumoniae,potentially exerting its action by regulating signaling pathways such as NF-κB and mitogen-activated protein kinase B through targeting TP53,TNF,BCL-2,IL-6,and NFκB1.