Study On The Effect Of Jinwei Decoction On Regulating The Sensitivity Of Chronic Obstructive Pulmonary Disease To Glucocorticoids Based On Network Pharmacolog

Objective:1.To analyze the pathways related to anti-inflammatory mechanisms in the treatment of chronic obstructive pulmonary disease with Jinwei decoction through network pharmacology theory.2.Based on the PI3/Akt/HDAC2 signaling pathway,investigate the regulation of Jinwei Tang on the sensitivity of COPD cells to glucocorticoids.Methods:(1)The active ingredients and target genes of Jinwei Decoction were screened by using the Systems pharmacology database and analysis platform(TCMSP)of traditional Chinese medicine and the bioinformatics analysis tools of BATMAN-TCM molecular mechanism of traditional Chinese medicine;Search for genes related to chronic obstructive pulmonary disease using the GeneCards,OMIM,and Drugbank databases;Obtain drug disease intersection genes by combining Jinwei Tang drug target genes with COPD disease related genes through Wayne diagram;Perform drug disease intersection gene protein interaction analysis(PPI)using the Protein Interaction Database(String),and screen core genes using the CytoNCA plugin in Cytoscape 3.7.2 software;Use R software to conduct Gene Ontology(GO)analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis on drug disease intersection genes,and visualize the bar chart and bubble graph of representative results.(2)Experimental study:A COPD model was constructed using cigarette smoke(CSE)to stimulate human pulmonary bronchial epithelial cells(BEAS-2B),and the concentration and time of CSE intervention in BEAS-2B cells were measured using the CCK8 method;Using the CCK8 method to detect the concentration time relationship of Jinwei Tang rat serum in improving the survival rate of COPD cell models;Using the CCK8 method to detect the toxicity of Jinwei Tang rat serum on BEAS-2B cells;ELISA method was used to detect the expression of IL-8 in blank control group,CSE blank model control group(model group),rat blank serum group,and rat Jinwei Tang drug serum group,to explore whether CSE can induce a decrease in glucocorticoid sensitivity in BEAS-2B cells,and whether Jinwei Tang rat drug serum can improve the decrease in glucocorticoid sensitivity in COPD cell models;Western blot method was used to determine the expression of PI3k,Akt,and HDAC2 proteins in cells of blank control group,CSE control group(model group),CSE+hormone group,Jinwei Tang serum+hormone group,and blank serum+hormone group.The aim was to explore the COPD cell model induced by CSE and the improvement of glucocorticoid sensitivity in COPD cells by Jinwei Tang rat serum.Results:(1)Jinwei Tang regulates 21 core proteins such as IL-6,TNF,VEGFA,EGF,and EGFR through 231 active ingredients of traditional Chinese medicine,participating in biological processes such as reactive oxygen species response,cellular response to oxidative stress,response to lipopolysaccharides,and PI3k Akt,TNF α、Signal pathways such as HIF-1 and IL-17 are used to treat chronic obstructive pulmonary disease.(2)CSE intervention in BEAS-2B cells can activate the PI3k/Akt signaling pathway and reduce the expression of HDAC2,while Jinwei Tang containing serum can intervene in this process and promote the expression of HDAC2.Conclusion:(1)Jinwei Tang may regulate the activity of HDAC2 by interfering with the PI3/Akt signaling pathway,enhancing the anti-inflammatory effect of glucocorticoids on COPD,and its mechanism may be related to Jinwei Tang’s intervention in PI3k Akt and TNFα、Related to signaling pathways such as HIF-1 and IL-17.(2)After experimental verification,it was found that cigarette smoke(CSE)can induce human bronchial epithelial cells(BEAS-2B)to construct a COPD model,leading to a decrease in glucocorticoid sensitivity in the COPD cell model.However,Jinwei Tang rat serum can regulate glucocorticoid sensitivity in COPD cells th rough the PI3/Akt/HDAC2 pathway.