Bioinformatics analysis unveils hub genes in the pathogenesis of sevoflurane anesthesia-induced respiratory...

Sevoflurane dose-dependently suppresses respiratory activity, yet its molecular mechanisms remain incompletely understood. In this study, we integrated transcriptomic data from the Gene Expression Omnibus and GeneCards to identify differentially expressed genes associated with sevoflurane anesthesia and respiratory depression. A protein-protein interaction network was constructed, and hub genes were screened using the MCC, Betweenness, Closeness, and MCODE algorithms. Functional associations of these hub genes were further explored using the GeneMANIA platform. Potential therapeutic compounds were predicted through the Connectivity Map (CMap) database. The effects of sevoflurane on ICAM1 expression and the intervention of PD-98059 were experimentally validated in SH-SY5Y cells. Ultimately, nine hub genes were identified, including MMP9, CXCL1, IL1B, NF-κB1, CXCL8, IL6, CCL2, ICAM1, and VCAM1. These genes were mainly enriched in pathways related to inflammatory responses, immune regulation, and chemotaxis. Increased infiltration of dendritic cells, MHC class I molecules, and neutrophils was observed in the sevoflurane-treated group. PD-98059 was predicted as a potential therapeutic candidate and was confirmed to reverse sevoflurane-induced upregulation of ICAM1. Overall, this study identifies key genes and inflammatory pathways associated with sevoflurane-induced respiratory suppression, providing new insights into its molecular mechanisms and potential therapeutic strategies.