Multi-Omics and Experimental Validation Identify GPX7 and Glutathione-Associated Oxidative Stress as Potential...

Ischemic stroke (IS) is the leading cause of disability and death worldwide, and its high incidence, disability and recurrence rates impose a heavy economic burden on families and society. Recent studies have shown that oxidative stress plays a key role in the pathophysiological mechanisms of ischemic stroke, not only participating in the onset and development of neuronal damage in the acute phase but also significantly influencing the long-term prognosis of ischemic stroke through molecular mechanisms, such as epigenetic modifications. However, the potential targets of oxidative stress-related genes in IS and their mechanisms of action remain to be elucidated. The aim of this study was to systematically analyse the function and significance of oxidative stress-related genes in IS. We obtained IS-related gene expression datasets from the GEO database and integrated known oxidative stress-related genes from the Genecards database for cross-analysis. Multidimensional feature screening using unsupervised consensus clustering and a series of machine learning algorithms led to the identification of the signature gene GPX7. The correlation between this gene and immune cell infiltration was assessed using MCPcounter and a potential therapeutic agent, glutathione, was identified. Binding was verified by molecular docking (MD) analysis. In addition, single-cell RNA sequencing data were analysed to further reveal expression in different cell types and its biological significance. Finally, we performed in vivo experiments using the Wistar rat middle cerebral artery occlusion (MCAO) model, and the results indicated that GPX7 plays a key role in IS, providing a new theoretical basis and potential intervention target for the precise treatment of IS.