The Protective Effects of Nebulized Metformin on Acute Lung Injury in Mice

To investigate the protective effects of metformin administered via nebulized inhalation on a mouse model of acute lung injury (ALI) induced by lipopolysaccharide (LPS).Methods A total of forty mice weighing 18-22 g were randomly assigned to four groups:①Control group (NC): Nebulized inhalation of phosphate-buffered saline (PBS);②Model group (LPS): Nebulized inhalation of LPS (50 mg/kg) for 24 hours;③Treatment group (Met+LPS): Metformin (150 mg/kg) was administered via nebulized inhalation 0.5 hours prior to LPS exposure, followed by nebulized inhalation of LPS for 24 hours;④Positive control group (DEX):Dexamethasone (5mg/kg) was administered orally 0.5 hours before LPS exposure,followed by nebulized inhalation of LPS for 24 hours. Lung CT images and histopathological changes in lung tissues were observed in each group. The levels of total protein and pro-inflammatory cytokines in bronchoalveolar lavage fluid were determined. Myeloperoxidase (MPO) activity in lung tissue homogenates was assessed, and the expression of AMPK/NF-κB genes in lung tissues was analyzed using RT-qPCR.Results In the LPS-induced ALI model, micro-CT revealed scattered patchy high-density shadows in both lungs of the mice. Hematoxylin and eosin (H&E) staining demonstrated severe alveolar inflammatory infiltration, significant destruction of lung tissue structure, markedly elevated levels of pro-inflammatory cytokines in BALF, enhanced MPO activity in lung tissues, decreased AMPK expression as detected by RT-qPCR, and increased NF-κB expression. These pathological changes were significantly alleviated in the mice pretreated with nebulized metformin.Conclusion Nebulized inhalation of metformin may ameliorate pulmonary pathological changes in mice with ALI by activating the AMPK signaling pathway.