基于微阵列数据和分子对接技术探讨青蒿鳖甲汤治疗儿童脓毒症急性肺损伤的作用机制OA

Objective To investigate the mechanism of Artemisiae Annuae Herba and Trionycis Carapax Decoction(mainly composed of Artemisiae Annuae Herba,Trionycis Carapax,Rehmanniae Radix,Anemarrhenae Rhizoma,and Moutan Cortex)in treating pediatric sepsis-induced acute lung injury(ALI)based on microarray data and molecular docking technology.Methods Microarray data of pediatric sepsis-induced ALI from the GEO database were analyzed using R software.Active components and corresponding targets of Artemisiae Annuae Herba and Trionycis Carapax Decoction were obtained from the TCMSP database,and a drug-compound-target network was constructed using Cytoscape 3.7.2.Venn diagrams were generated using online plotting tools to identify potential targets of the decoction for treating pediatric sepsis-induced ALI.A protein-protein interaction(PPI)network of common targets was constructed using the STRING database and Cytoscape 3.7.2 software.Common targets processed by the STRING database were imported into the Metascape database for Gene Ontology(GO)functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis.Molecular docking simulations were performed using Autodock Vina software,and the results were visualized using PyMol 2.4.0.Results A total of 487 differentially expressed genes(DEGs)were screened out,including 328 significantly upregulated genes and 159 significantly downregulated genes.The top 10 active components of Artemisiae Annuae Herba and Trionycis Carapax Decoction obtained from TCMSP were quercetin,kaempferol,luteolin,β-sitosterol,stigmasterol,gallic acid,catalpol,mangiferin,paeonol,and paeoniflorin.The drug-compound-target network consisted of 194 nodes and 322 edges,and 5 compounds had a degree≥10,indicating their key roles in the network.A total of 4 349 pediatric sepsis-induced ALI-related targets were obtained from Genecards/DisGeNET.After importing the targets of pediatric sepsis-induced ALI and the active components of Artemisiae Annuae et Carapacis Trionycis Decoction into the Venn diagram editing website,98 potential targets of the decoction for treating pediatric sepsis-induced ALI were identified.The PPI network of Artemisiae Annuae Herba and Trionycis Carapax Decoction and pediatric sepsis-induced ALI consisted of 98 nodes and 1 835 edges.The obtained top 10 core targets included nuclear factor erythroid 2-related factor 2(Nrf2),B-cell lymphoma-2(BCL-2),nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3),caspase 3(CASP3),hypoxia-inducible factor 1 αlpha(HIF1A),sirtuin 1(SIRT1),signal transducer and activator of transcription 3(STAT3),myelocytomatosis oncogene(MYC),serine/threonine-protein kinase 1(AKT1),and vascular endothelial growth factor A(VEGFA).GO functional enrichment analysis revealed that the biological processes involved in the treatment of pediatric sepsis-induced ALI by Artemisiae Annuae Herba and Trionycis Carapax Decoction included host-virus interaction,apoptosis,inflammatory response,regulation of circadian rhythm,chemotaxis,hemostasis,collagen degradation,blood coagulation,glycogen metabolism,and fibrinolysis.KEGG pathway enrichment analysis identified 158 signaling pathways,and the top 5 key pathways were the mitogen-activated protein kinase(MAPK)signaling pathway,phosphatidylinositol 3-kinase/protein kinase B(PI3K/AKT)signaling pathway,hypoxia-inducible factor 1(HIF-1)signaling pathway,interleukin-17(IL-17)signaling pathway,and tumor necrosis factor(TNF)signaling pathway.Molecular docking results demonstrated favorable binding interactions between quercetin and Nrf2,SIRT1,BCL-2,between kaempferol and NLRP3,AKT1,MYC,between luteolin and STAT3,CASP3,between β-sitosterol and BCL-2,VEGFA,and between paeoniflorin and SIRT1,HIF1A.Conclusion Artemisiae Annuae Herba and Trionycis Carapax Decoction exerts its therapeutic effects on pediatric sepsis-induced ALI probably through multiple targets and pathways.