Background: The incidence of sevoflurane-related adverse respiratory events in children with asthma is notably high. During different phases of sevoflurane anesthesia, asthmatic children's airways are exposed to varying concentrations of the anesthetic. However, the specific effects of different concentrations of sevoflurane on the developing airways with asthmatic hyperreactivity have not been systematically studied.
Methods: An ovalbumin (OVA)-induced juvenile rat asthma model was established to evaluate the impact of varying sevoflurane concentrations on airway irritation symptoms, ventilation, pathological scoring, and inflammation. Tandem mass tag (TMT)-based quantitative proteomics and bioinformatics analyses were conducted, with key protein expressions validated by western blot.
Results: Sevoflurane alleviated airway irritation symptoms in OVA-treated rats in a concentration-dependent manner. At 3.2 %, sevoflurane significantly reduced peribronchial inflammation, while 0.4 % sevoflurane exacerbated hypoxia, peribronchial injury, and inflammation. Proteomic analysis identified 54 overlapping differentially expressed proteins (DEPs), with three (serine protease inhibitor (SerpinA3L), major histocompatibility complex 1 (MHC1), and major histocompatibility complex 2 (MHC2)) being upregulated in the 3.2 % sevoflurane group but downregulated in the 0.4 % sevoflurane group. DEPs were predominantly linked to lysosomal and phagosomal pathways, as well as antigen processing and presentation. Three key hub proteins-cathepsin (CAT), vav guanine nucleotide exchange factor 1 (VAV1), and C-reactive protein (CRP)-were identified, and their expression levels were validated, matching the bioinformatics analysis results.
Conclusions: Our findings demonstrate that sevoflurane exerts opposing effects on the airways of juvenile asthmatic rats, depending on the concentration. MHC1, MHC2, and VAV1 emerged as crucial mediators of these differential effects, suggesting their potential as targets for understanding sevoflurane's impact on asthmatic airways.
Keywords: Asthma; Bioinformatics; Inflammation; Proteomics; Sevoflurane.
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