Wei Hong, Liu Tian-Hua, Zhang Li-Juan, Yan Wei, Ma Can, Lv Shi-Hua, Zeng Xian-Zhang, Li Wen-Zhi
Department of Anesthesiology, Hei Long Jiang Province Key Laboratory of Research on Anesthesiology and Critical Care Medicine, Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150081, P.R. China.
Department of Anesthesiology, Taizhou Hospital of Zhe Jiang Province, Taizhou, Zhejiang 317000, P.R. China.
Mol Med Rep. 2025 Nov;32(5). doi: 10.3892/mmr.2025.13652. Epub 2025 Aug 14.
Diabetes mellitus (DM) exacerbates lung ischemia‑reperfusion (IR) injury and leads to poor survival in lung transplantation recipients. Metformin protects a number of tissues from IR injury. The present study aimed to investigate the effect of metformin on diabetic lung IR injury and the potential mechanisms. Rats with type 2 DM were exposed to metformin with or without administration of EX527, an inhibitor of the silent information regulator 1 (SIRT1) pathway, following lung transplantation. Lung function, alveolar‑capillary permeability, inflammatory response, oxidative stress, cell apoptosis, mitochondrial function, mitochondrial biogenesis key proteins and the SIRT1 signaling pathway were assessed. The effect of metformin on diabetic lung IR injury was evaluated by ELISA, oxidative stress assays, immunofluorescence, flow cytometry, TUNEL assay and western blotting. The results demonstrated that DM was associated with a significant increase in the IR‑induced alveolar‑capillary permeability, inflammatory response, oxidative stress and cell apoptosis. Furthermore, DM was associated with a significant decrease in mitochondrial function and biogenesis, SIRT1 expression and lung function. Metformin treatment markedly attenuated diabetic lung IR injury by alleviating the inflammatory response, oxidative stress and cell apoptosis, preserving mitochondrial function, and promoting mitochondrial biogenesis. However, EX527 inhibited the protective effect of metformin. In conclusion, metformin alleviated the inflammatory response, oxidative stress and cell apoptosis, preserved mitochondrial function, and promoted mitochondrial biogenesis via the activation of the SIRT1 pathway in diabetic lung IR injury.
糖尿病（DM）会加剧肺缺血再灌注（IR）损伤，并导致肺移植受者的生存率降低。二甲双胍可保护多种组织免受IR损伤。本研究旨在探讨二甲双胍对糖尿病性肺IR损伤的影响及其潜在机制。将2型糖尿病大鼠在肺移植后给予或不给予沉默信息调节因子1（SIRT1）途径抑制剂EX527的情况下暴露于二甲双胍。评估肺功能、肺泡-毛细血管通透性、炎症反应、氧化应激、细胞凋亡、线粒体功能、线粒体生物发生关键蛋白和SIRT1信号通路。通过ELISA、氧化应激测定、免疫荧光、流式细胞术、TUNEL测定和蛋白质印迹法评估二甲双胍对糖尿病性肺IR损伤的影响。结果表明，DM与IR诱导的肺泡-毛细血管通透性、炎症反应、氧化应激和细胞凋亡的显著增加有关。此外，DM与线粒体功能和生物发生、SIRT1表达及肺功能的显著降低有关。二甲双胍治疗通过减轻炎症反应、氧化应激和细胞凋亡、保留线粒体功能以及促进线粒体生物发生，显著减轻了糖尿病性肺IR损伤。然而，EX527抑制了二甲双胍的保护作用。总之，二甲双胍在糖尿病性肺IR损伤中通过激活SIRT1途径减轻了炎症反应、氧化应激和细胞凋亡，保留了线粒体功能，并促进了线粒体生物发生。
