To Explore the Mechanism of Fuzheng Touxie Jiedu Decoction(扶正透邪解毒方)in Treating Pseudomonas Aeruginosa Pneumonia Based on Network Pharmacology and Cell Experiments
Objective:To screen the active compounds of Fuzheng Touxie Jiedu decoction against Pseu-domonas aeruginosa pneumonia,and to investigate the mechanism of Fuzheng Touxie Jiedu decoction in treating Pseudomonas aeruginosa pneumonia by in vitro cell experiment.Methods:GeneCard and OMIM databases were used to screen the disease targets of Pseudomonas aeruginosa pneumonia,to identify the common potential targets of active ingredients of Fuzheng Touxie Jiedu decoction and Pseudomonas aeruginosa pneumonia.The protein-protein interaction(PPI)network was constructed by String database and Cytoscape software.Gene ontology(GO)function and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis were performed by DAVID database.In vitro cell experiments,CD4+T cells were co-cultured with multi-drug resistant Pseudomonas aeruginosa.After the intervention of Fuzheng Touxie Jiedu decoction containing drug-containing serum,RT-PCR was used to detect tumor protein P53(TP53)mRNA,serine/threonine protein kinase 1(AKT1)mRNA,interleukin-6(IL-6)mRNA,interleukin-10(IL-10)mRNA,interleukin-1β(IL-1 β)and tumor necrosis factor-α(TNF-α)mRNA in CD4+T cells.Western blotting was used to detect the protein expression of IL-6,TNF-α,AKT1,IL-1β,TP53 and IL-10 in CD4+Tcells.Results:A total of 226 potential active ingredients and 93 potential targets were screened.TP53,AKT1,IL-6,IL-10,IL-1β and TNF-α were the key targets of Fuzheng Touxie Jiedu decoction in the treatment of Pseudomonas aeruginosa pneumonia.Fuzheng Touxie Jiedu decoction mainly plays a role in the treatment of Pseudomonas aeruginosa pneumonia through inflammatory factors,chemokines,immune regulation and other signaling pathways.Fuzheng Touxie Jiedu decoction containing serum could reduce the expression of IL-6 mRNA,TNF-α mRNA,AKT1 mRNA and IL-1β mRNA in CD4+T cells(P＜0.01),and promote the expression of TP53 mRNA and IL-10 mRNA in CD4+T cells(P＜0.01).Fuzheng Touxie Jiedu decoction containing serum could reduce the protein expressions of IL-6,TNF-α,AKT1 and IL-1βin CD4+T cells(P＜0.05),and promote the expression of TP53 and IL-10 protein in CD4+T cells(P＜0.05).Conclusions:Fuzheng Touxie Jiedu decoction can inhibit pulmonary infection by regulating the expression of TNF-α,AKT1,TP53,IL-10 and other key factors to treat Pseudomonas aeruginosa pneumonia.
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