Desflurane post-conditioning inhibits HMGB1 nucleocytoplasmic translocation via the SIRT1/HMGB1 axis to attenuate hepatic ischemia-reperfusion-induced acute lung injury in young rats.

Acute lung injury (ALI) is a common clinical complication in pediatric patients undergoing perioperative liver transplantation, and therapeutic approaches are limited. While desflurane exhibits organ-protective potential, its specific efficacy against hepatic ischemia-reperfusion (HIR)-induced ALI in the developing lung, as well as the underlying molecular mechanisms, remain poorly understood. This study aimed to investigate the protective effects of desflurane and delineate the regulatory pathways involved. 2 week-old Sprague-Dawley rats were subjected to 70% warm HIR to simulate pediatric liver transplantation. Desflurane was administered at the onset of reperfusion. The severity of lung injury, inflammatory responses, and relevant intracellular signaling pathways were evaluated using histological and molecular analyses. In vitro, NR8383 alveolar macrophages underwent oxygen-glucose deprivation (OGD) reoxygenation to further verify the underlying mechanisms. The results showed that desflurane post-conditioning significantly improved ALI induced by HIR, characterized by reduced acute lung injury scores and inhibited release of albumin, tumor necrosis factor (TNF)-α, macrophage inflammatory protein (MIP) -2 in bronchoalveolar lavage fluid, and HMGB1 in serum. Furthermore, we found that desflurane could upregulate the silent information regulator 2-related enzyme (SIRT) 1 level and inhibit the nucleocytoplasmic translocation and acetylation of HMGB1 and its related signaling pathways. Desflurane upregulated SIRT1 expression, which directly mediated the deacetylation of HMGB1 at the K29/K177 residues in vitro. Notably, the above-mentioned effects of desflurane on ALI were markedly attenuated by Ex527, a specific inhibitor of SIRT1, both in vivo and in vitro. Our data indicate that desflurane post-conditioning attenuates HIR-induced lung injury in young rats by restoring SIRT1-mediated HMGB1 deacetylation and provides a new research direction for the clinical development of safe and effective perioperative ALI prevention and treatment strategies in pediatric liver transplantation.