Screening Of Key Genes Of Myocardial Infarction And Targets Of Invigorating Qi And Blood-activating Drugs Based On Bioinformatics Analysis

Background:Myocardial infarction(MI)is a serious cardiovascular disease with a high fatality rate.The main reason for its occurrence is the sudden occlusion of the heart and coronary arteries.The myocardium causes local necrosis due to rapid and continuous ischemia/hypoxia.The prevalence of cardiovascular diseases in my country continues to rise,and the death rate of cardiovascular diseases is still the first.Among them,MI is an important fatal factor.In recent years,with the development of transcriptomics,a large amount of transcriptome data has been generated,and the methods of bioinformatics analysis have been gradually enriched.Using these data for bioinformatics analysis to find targets for disease diagnosis and treatment has become a research hotspot.In MI-related research,there is also a large amount of transcriptome sequencing data that urgently needs further analysis and utilization.Traditional Chinese medicine is widely used in the treatment of cardiovascular diseases.The medicines for Yiqi Huoxue Decotion with Radix Astragali,Radix Angelicae sinensis,Radix Ginseng,Radix chuanxiong and Radix Notoginseng have shown good clinical effects in the treatment of myocardial infarction.Due to the characteristics of multi-components,multi-targets,and multiaction pathways of traditional Chinese medicine and its compound prescriptions,the material basis and mechanism of action for the treatment of MI by Yiqi Huoxue Decotion is still unclear.Therefore,this study intends to use the weighted gene co-expression network analysis(WGCNA)method to mine the whole transcription sequencing data of MI in order to screen the key targets of MI,and the method of network pharmacology to screen the Yiqi Huoxue Decotion.The important active ingredients in the treatment of MI,the two parts of the content are combined to study the molecular mechanism of the treatment of MI by the medicine for Yiqi Huoxue Decotion.Objective:Based on the weighted gene co-expression network analysis and network pharmacology,the key genes of myocardial infarction and the important active ingredients of the medicine for Yiqi Huoxue Decotion are screened,the transcription regulation network is constructed and the function enrichment analysis is performed,and the treatment of myocardium by the medicine for Yiqi Huoxue Decotion at the level of system bioinformatics analysis the molecular mechanism of infarction is discussed.Methods:1.Weighted gene co-expression network analysisDownload myocardial infarction transcriptome sequencing data sets GSE132143 and GSE48060 from GEO.Use the R language WGCNA software package to analyze the data set GSE132143 and identify the co-expression modules.Correlate the trait information and screen out the key modules closely related to myocardial infarction.Use clusterProfiler software package to carry out GO and KEGG enrichment analysis on key modules.Identify the transcription factors and non-coding RNAs of key modules and construct a transcriptional regulatory network.Use Cytoscape to construct a protein interaction(PPI)network of key modules and identify the key genes in the modules.Use ROC curve analysis and the differential genes of GSE132143 and GSE48060 to verify the key genes screened out.2.Network pharmacology analysisObtain and screen the chemical components of Radix Astragali,Radix Angelicae sinensis,Radix Ginseng,Radix chuanxiong and Radix Notoginseng through TCMSP,PubChem and other databases,and then use SwissTargetPrediction to predict the target of each component,and use the target of the HERB database as a supplement.The differential genes of GSE132143 and the targets obtained from databases such as GeneCards,OMIM,DrugBank,TTD and HERB are used as targets related to myocardial infarction.Use Metascape database to conduct GO and KEGG enrichment analysis of the intersection genes.Use the String database to construct the PPI network,import the results into Cytoscape,and use the MCODE plug-in to screen the key genes of the important module sets in the network.Based on Cytoscape,the component-target network and component-target-pathway network were constructed to screen the important active components of myocardial infarction with the effects of Yiqi Huoxue Decotion.3.Molecular docking verificationDownload the crystal structure of each target from the PDB database,and obtain the threedimensional structure of each component from TCMSP.Autodock 4.2 is used for molecular docking,and the components with better docking activity are selected according to the lowest binding energy and the target is visualized using Pymol.Results:1.Weighted gene co-expression network analysis resultsThe four key modules of myocardial infarction,black?blue?yellow and magenta,were screened out through weighted gene co-expression network analysis.The functional enrichment analysis of each module found that the genes in the module are mainly involved in the regulation of kinase activity,protein processing and energy metabolism,and are involved in signal pathways such as oxidative phosphorylation,PI3K-Akt,Notch,and tumor necrosis factor.Construct transcription factor regulatory network,long non-coding RNA and microRNA regulatory network,and screen out HSBP1,RPL7,ENO1,MORC3,ZNF24,POLR2B,CUL5,COPS3,PRDX3,SLC30A9,HMGB1,MTDH,ERC1,BMI1,MBD2,LARP4B Fourteen important transcription factors and four long non-coding RNAs such as TTTY14,SNHG5,FGD5-AS1 and MAPKAPK5-AS1 occupy the core position in the related co-expression network of MI.By constructing the PPI network of each module,RPL7,HSBP1,CDC42,DNM1L,MORC3,PRKAA1,HIF1A,TFAM,SOD2,BIRC2,DIS3,PRDX3,EDN1,CAB39,MBD2,BECN1 and other genes are screened out as the key genes in the module.Among them,DNM1L,PRKAA1,TFAM,DIS3,and PRDX3 were verified by ROC curve analysis and differential gene analysis as the key genes finally screened out.All genes were down-regulated in the data GSE132143.2.Network pharmacology analysis resultsBased on network pharmacology to obtain MI targets for Yiqi Huoxue Decotion,construct a PPI network and screen out important MCODE modules in the network,perform network topology analysis on the modules and screen out the core targets in the modules as MAPK1,PIK3CA,AKT1,APP.MAPK3,SRC,STATS,TP53.The functional enrichment analysis of MI targets for the effects of Yiqi Huoxue Decotion found that the targets are mainly enriched in PI3K-Akt signaling pathway,lipids and atherosclerosis,Rapl signaling pathway,fluid shear stress and atherosclerosis,cGMP-PKG signal pathway,HIF-1 signal pathway and other signal pathways.By constructing a component-target network and a component-target-pathway network,the two networks were analyzed and the results were compared,and the main active components of MI of the medicine for Yiqi Huoxue Decotion were screened out as Deoxyharringtonine,Myricanone,Liquiritigenin,Jaranol.3.Results of molecular docking verificationThe key genes selected by the weighted gene co-expression network analysis and the important components of the Yiqi Huoxue Decotion selected by the network pharmacology were verified by molecular docking.The docking results showed that the important components of the medicine for replenishing qi and activating blood,Deoxyharringtonine,Myricanone,Liquiritigenin,Jaranol as small molecule ligands and key genes DNM1L,PRKAA1,TFAM,DIS3,PRDX3 encoded receptor proteins.The lowest binding energy is negative,and can form a stable hydrogen bond structure.DNM1L and Liquiritigenin,PRKAA1 and Deoxyharringtonine,TFAM and Jaranol,DIS3 and Myricanone,PRDX3 and Deoxyharringtonine have better binding activity than other ingredients.Conclusion:Based on the weighted gene co-expression network analysis and network pharmacology,this study screened the key genes of myocardial infarction and the important active ingredients of the Yiqi Huoxue Decotion,and verified them through molecular docking.The results showed that the Yiqi Huoxue Decotion may pass DNM1L,PRKAA1,TFAM,DIS3 and PRDX3 play a role in the prevention and treatment of myocardial infarction,and these targets have the value as potential biomarkers.This research is mainly based on data analysis and preliminary verification through existing research results and data resources.Therefore,further biological experiments are needed to verify the research results.