Sheng Li Xue Bao. 2026 Apr 25;78(2):452-462. doi: 10.13294/j.aps.2025.0070.
ABSTRACT
This study aimed to investigate the effects of lipocalin-2 (LCN2) gene knockout (LCN2KO) on cecal ligation and perforation (CLP)-induced lung injury and ferroptosis in septic mice, and further to clarify the potential role of the Toll-like receptor 4 (TLR4)/nuclear factor κB (NF-κB) pathway. A CLP model was established using LCN2KO mice. The levels of serum interleukin-6 (IL-6) and IL-1β were measured by ELISA. The contents of malondialdehyde (MDA) and glutathione (GSH) in lung tissue were determined using the corresponding assay kits. Reactive oxygen species (ROS) levels in lung tissue were detected using dihydroethidium (DHE) fluorescent probe. The expression levels of ferroptosis-related proteins in lung tissue were assessed by Western blot. The results showed that, compared to wild-type (WT)-Sham group, WT-CLP group exhibited significant lung tissue damage, elevated serum IL-6 and IL-1β levels, increased MDA content and ROS level, decreased GSH content, up-regulated protein expression levels of LCN2 and TLR4, increased p-P65/P65 ratio, and significantly down-regulated protein expression levels of ferroptosis suppressor protein 1 (FSP1) and glutathione peroxidase 4 (GPX4). LCN2KO reversed these changes induced by CLP. Both TLR4 inhibitor TAK-242 and NF-κB inhibitor PDTC down-regulated lung LCN2 protein expression, reversed sepsis-induced ferroptosis and lung injury, which is similar to the role of LCN2KO. These results suggest that LCN2KO may ameliorate lung injury in sepsis-induced mouse model by attenuating ferroptosis through modulating the TLR4/NF-κB signaling pathway.
PMID:42014343 | DOI:10.13294/j.aps.2025.0070