Sevoflurane, a widely used anesthetic, has been reported to modulate inflammatory responses in sepsis models. However, its influence on autophagy-related neutrophil extracellular trap (NET) formation and early organ injury during sepsis remains unclear. Both neutrophil autophagy and NET formation are closely involved in sepsis-associated inflammation and tissue damage. We examined the effects of sevoflurane on pathological and inflammatory changes in a cecal ligation and puncture-induced sepsis model in Sprague-Dawley rats. Pathological changes in lung, kidney, and heart tissues were assessed by hematoxylin and eosin staining. Enzyme-linked immunosorbent assay (ELISA) was used to measure inflammatory cytokines and NET-related markers, including myeloperoxidase (MPO), neutrophil elastase (NE), histone H3 (H3), and their corresponding DNA complexes in bronchoalveolar lavage fluid (BALF). Western blotting analyzed the expression of the autophagy-related proteins LC3 and p62 in neutrophils. Rapamycin was applied as an autophagy activator to explore its role in sevoflurane-associated effects. Sevoflurane was associated with milder early pathological and inflammatory changes, with the most consistent findings observed at 0.75% for 4 h. Sevoflurane attenuated inflammatory cell infiltration and tissue injury in lung, kidney, and heart tissues. Immunofluorescence staining showed fewer citrullinated histone H3 and MPO double-positive cells in lung tissue, indicating reduced NET-related signals. Rapamycin partially reversed several of these changes. Sevoflurane may modulate early inflammatory injury in sepsis by influencing NET formation and autophagy-related processes.
Wang et al. (Sun,) studied this question.