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.

本研究旨在探讨雾化吸入二甲双胍对脂多糖（lipopolysaccharide, LPS）诱导的急性肺损伤（acute lung injury, ALI）小鼠模型的保护作用。
实验方法：选取40只体重18~22g的小鼠，随机分为4组：①对照组（NC）：雾化吸入磷酸盐缓冲液（phosphate-buffered saline, PBS）；②模型组（LPS）：雾化吸入LPS（50mg/kg），持续造模24小时；③治疗组（Met+LPS）：于LPS暴露前0.5小时雾化吸入二甲双胍（150mg/kg），随后继续雾化吸入LPS 24小时；④阳性对照组（DEX）：于LPS暴露前0.5小时口服给予地塞米松（5mg/kg），随后雾化吸入LPS 24小时。各组均开展以下检测：小鼠肺CT影像与肺组织病理变化；支气管肺泡灌洗液（bronchoalveolar lavage fluid, BALF）中总蛋白与促炎细胞因子水平；肺组织匀浆的髓过氧化物酶（myeloperoxidase, MPO）活性；采用RT-qPCR分析肺组织中AMPK/NF-κB基因的表达水平。
实验结果：在LPS诱导的ALI小鼠模型中，微型CT（micro-CT）检测显示小鼠双肺可见散在斑片状高密度阴影；苏木精-伊红（hematoxylin and eosin, H&E）染色可见肺泡严重炎性浸润、肺组织结构显著破坏；BALF中促炎细胞因子水平显著升高，肺组织MPO活性增强；RT-qPCR检测显示肺组织AMPK表达下调，NF-κB表达上调。经雾化吸入二甲双胍预处理的小鼠，上述病理损伤均得到显著缓解。
研究结论：雾化吸入二甲双胍可通过激活AMPK信号通路，改善ALI小鼠的肺部病理损伤。