Spermidine mitigates lipopolysaccharide-induced acute lung injury by enhancing autophagic flux.

The primary pathological characteristics of acute lung injury (ALI), comprise the dysfunction of the endothelial barrier, primarily due to the death of pulmonary microvascular endothelial cells (PMVECs), with pyroptosis identified as the principal mechanism underlying lipopolysaccharide (LPS)-induced endothelial cell death. Current research suggests that autophagy suppresses pyroptosis. Spermidine (SPD), an endogenous polyamine, is known for its potent ability to induce autophagy. Nevertheless, the impact of SPD on LPS-induced ALI and PMVEC pyroptosis remains unclear. In the present study, an ALI model was established through an intratracheal injection of LPS. SPD treatment significantly alleviated LPS-induced lung injury in mice and reduced caspase-1 activation and gasdermin D N-terminal expression in lung tissues. To further investigate the mechanism, PMVEC pyroptosis was modeled using LPS combined with nigericin. In vitro experiments revealed suppressed autophagic flux under pyroptotic conditions, while SPD restored autophagic flux and attenuated PMVEC pyroptosis. These findings indicated that SPD protects against endothelial cell damage, partially through autophagic flux restoration.