| Objective: To explore the molecular mechanism of Yiqi-Huatan-Quyu Formula in the treatment of chronic intermittent hypoxia-induced myocardial injury based on network pharmacology and proteomics.Methods: The experimental steps are as follows:(1)Inquire the ingredients of YiqiHuatan-Quyu Formula through TCMSP database and screen the chemical components contained in Yiqi-Huatan-Quyu Formula according to DL?0.18,OB?30% and Lipinski rules.Meanwhile,TCMSP database was used to construct the target database of small molecule compounds of Yiqi-Huatan-Quyu Formula.The published literature on "genes,polymorphisms and biomarkers" was searched in the Pub Med,MEDLINE and Embase search engines,and the Dis Ge NET database and the NCBI Gene database were further searched for disease genes.Establish a database for further analysis.The Metascape database was used for GO function enrichment and Kyoto Gene and Genome Encyclopedia Path Enrichment(KEGG)analysis to obtain functional and pathway enrichment results.The main action pathway of Yiqi-Huatan-Quyu Formula in the treatment of OSAHS-related myocardial injury was obtained.The enrichment analysis results were visualized by cytoscape.(2)Establishment of animal models: animals were divided into 3 groups: 6 in the normal control group,6 in the chronic intermittent hypoxia group,and 6 in the intermittent interventional group with Yiqi-Huatan-Quyu Formula.Quantitative proteomics based on i TRAQtechnology was used to analyze each group of myocardial tissue,and bioinformatics analysis and annotation of the Uni Prot protein database(http://www.uniprot.org/)was used to functionally annotate the identified proteins.Blast2 GO software(v4.5 pipeline5)is used to describe the three entities of molecular function,cell location and biological process.The KEGG database is used to analyze the interactions between the identified proteins and the signaling pathways involved.GO enrichment analysis was used to find entries that were significantly enriched in differential proteins.Results:(1)Results of network pharmacology analysis: 263 potential active ingredients of Yiqi-Huatan-Quyu Formula with OB?30% and DL?0.18,and 248 human genes of OSASH patients.The in vivo response network of Yiqi-Huatan-Quyu Formula against OSASH was constructed by using String database.A hierarchical network of functional classification of GO molecules and GO biological processes and KEGG pathway enrichment analysis were constructed using the metascape database for interacting genes.It has been found that Yiqi-Huatan-Quyu Formula could regulate the abnormalities of obesity and glycolipid metabolism,cardiovascular system,inflammation and central neurotransmitters through targeted regulation and pass the interleukin-4 and interleukin-13 signaling,cell-to-lipid reaction,cell-to-organic cyclic compound reaction,and negative regulation of apoptotic signaling pathway.Tumor necrosis factor response,positive regulation of the MAPK cascade,regulation of vesicle-mediated trafficking and regulation of inflammatory responses could counteract chronic intermittent hypoxia-induced inflammatory responses.(2)i TRAQquantitative proteomics was used to identify 839 differentially expressed proteins and five significant proteins Anxa5,Serpina1,Myh6,Adipoq,Cryz in rats with intermittent intermittent hypoxic rats and Yiqi-HuatanQuyu Formula.It was found that the differential proteins of Yiqi Huayu Recipe after intervention in rat myocardial injury were mainly involved in endoplasmic reticulum stress signaling pathway,actin-related pathway and PI3K/Akt signaling pathway.Bioinformatics analysis of differential protein interaction networks was performed from molecular function,cell localization,and biological pathways,which Metascape analysis shows that the differential protein interaction network is complex.Conclusions:(1)The main effective components of Quercetin and luteolin were screened by network pharmacology.Also,Heat shock protein 90(HSP90)?PPAR??and core targets of prostagnatin peroxide synthase 2(PTGS2)can both act on inflammatory responses.The analysis predicts that strong anti-inflammatory components play an important role in the treatment of obstructive sleep apneaassociated myocardial injury with Yiqi-Huatan-Quyu Formula.(2)Combined with the quantitative proteomics of i TRAQ,it is further recognized that the differential proteins of Yiqi-Huatan-Quyu Formula after intervention of myocardial injury in rats are mainly involved in endoplasmic reticulum stress signaling pathway,actin-related pathway,PI3K/Akt signal pathway regulation related to anti-myocardial injury. |
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