急性缺血性心肌病药物靶标发现与实验验证研究

	急性缺血性心肌病药物靶标发现与实验验证研究; The Finding of Drug Target for Acute Ischemic Cardiomyopathy and Experimental Verification Study
	田娇
导师	刘树柏
摘要	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, 11 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 ISCM.However, the specific mechanism of the four genes in ISCM still needs to be further explored
	2021-05
文献类型	学位论文
条目标识符	http://ir.kib.ac.cn/handle/151853/74549
专题	昆明植物所硕博研究生毕业学位论文
推荐引用方式 GB/T 7714	田娇. 急性缺血性心肌病药物靶标发现与实验验证研究, The Finding of Drug Target for Acute Ischemic Cardiomyopathy and Experimental Verification Study[D],2021.

条目包含的文件
文件名称/大小	文献类型	版本类型	开放类型	使用许可
田娇-田娇—论文（所里）fee866d8（2834KB）	学位论文		限制开放	CC BY-NC-SA	请求全文