| Ischemic cardiomyopathy（ISCM）is a disease caused by insufficient blood supply and oxygen supply to the myocardium,which cannot meet its metabolic needs.It is a major disease that seriously endangers the life and health of Chinese people at present.The adverse prognosis and therapeutic effect of surgical interventional therapy and drug therapy make the treatment of ISCM more difficult.With the development of the next generation sequencing technology,bioinformatics and multiomics have become important methods for precision medicine research.Therefore,the exploration,identification and verification of new ideal biomarkers will be of great significance for the diagnosis and treatment of ISCM and the development of targeted drugs.In this study,the human ISCM gene expression profile was obtained from the NCBI gene expression database GEO,and the weighted gene co-expression network analysis（WGCNA）was used to construct the co-expression network module,and the key modules related to the clinical parameters of ISCM were screened to determine the high-weighted hub genes in the key modules.David and KEGG databases were used for gene functional annotation and pathway enrichment analysis of related genes in key modules,and the pathways and mechanisms involved in hub genes were found.Furthermore,the STRING database was used to construct protein-central gene interaction network（PPI）analysis to identify interactions between central genes.RT-qPCR,immunohistochemistry,and serum were used to detect the differential expression of hub genes in the heart tissue of ischemic rats.The results showed that through the co-expression network analysis of WGCNA,a total of 23 gene expression modules were identified,among which Megreen module was the key module with stronger correlation with ischemic cardiomyopathy（ISCM）,and 11 hub genes with the strongest correlation with ISCM were found from this module.The results of gene functional annotation and enrichment analysis showed that the strongest correlation with ISCM was related to apoptosis,cell immunity,inflammation regulation,cell proliferation and other pathways.Myocardial ischemia rat model is established for RT-qPCR,immunohistochemical,serum factor test results showed that the gene expression of mRNA and protein expression level,compared with control group,1 1 hub genes have four genes has significant differences in expression,which,known in the ISCM model group significantly reduced,IFI44L,IFIT2,IFIT3 three genes in model group increased significantly.In summary,in this study,we found four hub genes significantly related to ISCM,which are mainly involved in two biological processes of cell apoptosis and immune response.The differential expression of the four genes was verified by myocardial ischemia rat model,which may become biomarkers for future clinical diagnosis and research of ISCMHowever,the specific mechanism of the four genes in ISCM still needs to be further explored.The innovation and significance of this study:1.In this study,for the first time,four key genes related to WGCNA were identified by the association between WGCNA and the clinical traits of ISCM,which mainly regulate ISCM through the biological processes of apoptosis,inflammatory response and immune response.2.In this study,we established a rat model of myocardial ischemia to further verify the results of bioinformatics analysis.Four key genes were significantly differentially expressed in rat heart tissue.3.The myocardial ischemia rat model successfully constructed in this study was consistent with the indicators of clinical myocardial ischemia patients through detection,and was successfully applied to gene screening in this paper,which can be used as an animal model for ISCM research. |
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