Open Access

Metformin alleviates lung ischemia‑reperfusion injury via the SIRT1 pathway following lung transplantation in diabetic rats

  • Authors:
    • Hong Wei
    • Tian-Hua Liu
    • Li-Juan Zhang
    • Wei Yan
    • Can Ma
    • Shi-Hua Lv
    • Xian-Zhang Zeng
    • Wen-Zhi Li
  • View Affiliations

  • Published online on: August 13, 2025     https://doi.org/10.3892/mmr.2025.13652
  • Article Number: 287
  • Copyright: © Wei et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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.
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November-2025
Volume 32 Issue 5

Print ISSN: 1791-2997
Online ISSN:1791-3004

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Spandidos Publications style
Wei H, Liu T, Zhang L, Yan W, Ma C, Lv S, Zeng X and Li W: Metformin alleviates lung ischemia‑reperfusion injury via the SIRT1 pathway following lung transplantation in diabetic rats. Mol Med Rep 32: 287, 2025.
APA
Wei, H., Liu, T., Zhang, L., Yan, W., Ma, C., Lv, S. ... Li, W. (2025). Metformin alleviates lung ischemia‑reperfusion injury via the SIRT1 pathway following lung transplantation in diabetic rats. Molecular Medicine Reports, 32, 287. https://doi.org/10.3892/mmr.2025.13652
MLA
Wei, H., Liu, T., Zhang, L., Yan, W., Ma, C., Lv, S., Zeng, X., Li, W."Metformin alleviates lung ischemia‑reperfusion injury via the SIRT1 pathway following lung transplantation in diabetic rats". Molecular Medicine Reports 32.5 (2025): 287.
Chicago
Wei, H., Liu, T., Zhang, L., Yan, W., Ma, C., Lv, S., Zeng, X., Li, W."Metformin alleviates lung ischemia‑reperfusion injury via the SIRT1 pathway following lung transplantation in diabetic rats". Molecular Medicine Reports 32, no. 5 (2025): 287. https://doi.org/10.3892/mmr.2025.13652