Screening and verification of drugs targeting myocardial ischemia-reperfusion injury.

This study focuses on the research of the molecular mechanism of myocardial ischemia-reperfusion injury (MIRI) and the exploration of treatment methods. Firstly, through the analysis of differentially expressed genes (DEGs) in 2 datasets, GSE108940 and GSE160516, 229 DEGs were identified. Further, by using the least absolute shrinkage and selection operator regression and random forest analysis, 3 key genes, FAS, PPARA, and FGF9, were screened out. To validate the reliability of these genes, their expression levels were observed in the merged set, experimental set, and validation set. It was found that FAS was highly expressed in the MIRI group, while PPARA and FGF9 were lowly expressed in the MIRI group, and these results were verified in the validation set. In addition, the receiver operating characteristic curve analysis demonstrated that FAS, PPARA, and FGF9 had good diagnostic values, with the area under the curve all >0.8. The study also explored the signaling pathways and molecular mechanisms in MIRI. The Gene Ontology analysis of the DEGs was mainly enriched in responses to interleukin-1, major histocompatibility complex protein complex, and chemokine activity. The Kyoto Encyclopedia of Genes and Genomes enrichment analysis showed that the DEGs were associated with the interaction between viral proteins and cytokines and their receptors, rheumatoid arthritis, and influenza A. The results of cell experiments showed that in the hypoxia/reoxygenation model, the cell viability decreased, and the contents of cTnI, creatine kinase, and lactate dehydrogenase were relatively high. After the administration of the candidate drugs resveratrol and GW4064, the cell viability was significantly improved, and the contents of cTnI, creatine kinase, and lactate dehydrogenase were reduced, indicating a significant effect on repairing damaged cells. Through Western blotting and immunofluorescence techniques, it was found that resveratrol and GW4064 could significantly decrease the expression of FAS and increase the expression of PPARA and FGF9 (P†<†.01), suggesting that these drugs may have potential therapeutic effects on MIRI. Overall, this study not only provides a new perspective for understanding the molecular mechanism of MIRI but also offers valuable clues for the development of new treatment strategies.