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Background <p>Lung ischemia-reperfusion injury (LIRI) is associated with a variety of postoperative complications and affects patient prognosis. β-Nicotinamide mononucleotide (NMN) has attracted much attention due to its potential role in cellular energy metabolism and antioxidant properties. Exploring the mitigating role of NMN in ischemia-reperfusion injury after lung transplantation is crucial for improving lung transplantation success and patient quality of life.</p> Methods <p>A LIRI model was established using the mouse left lung portal clamp method, and the cold ischemia-reperfusion (CI/R) model with BEAS-2B cells in vitro was used to simulate the lung transplantation environment. The protective effect of NMN against lung ischemia-reperfusion injury was analyzed by histopathology, ELISA, immunofluorescence, Western blot and RT-PCR. Combined multi-omics profiling were used to study the mechanisms by which NMN attenuated lung ischemia-reperfusion injury.</p> Results <p>NMN significantly attenuated ischemia-reperfusion-induced structural abnormalities, pulmonary edema, inflammatory infiltration and oxidative stress injury in mouse lung tissue. Similarly, NMN attenuated CI/R-induced oxidative stress and inflammatory responses in BEAS-2B cells. Based on multi-omics analysis, we found that NMN ameliorated the apoptosis after ischemia/reperfusion through down-regulation of cleaved Caspase 3, BAX and up-regulation of BCL-2. Moreover, NMN also affected mitochondrial metabolic processes, including promoting mitochondrial oxidative phosphorylation, increasing ATP synthesis, enhancing mitochondrial complex activity, decreasing ROS generation, slowing down the decrease of mitochondrial membrane potential, and inhibiting the opening of the mitochondrial membrane permeability transition pore. Mechanistically, we found that NMN attenuates inflammation and oxidative damage through activation of the SIRT1 and NF-κB signaling pathways, and that SIRT1-specific inhibition of EX527 reversed these protective effects of NMN against inflammation and oxidative damage in vivo and in vitro.</p> Conclusion <p>NMN has a protective effect on inflammation and oxidative damage induced by ischemia-reperfusion injury after lung transplantation, and the SIRT1/NF-κB pathway may be involved in one of the mechanisms of the protective effect.</p>

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β-Nicotinamide mononucleotide activates the SIRT1/NF-κB pathway to alleviate ischemia reperfusion injury after lung transplantation

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年11月25日

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  • Ganggui Zhu,
  • Qiaxuan Li,
  • Qifeng Yao,
  • Jin Zhao,
  • Shuo Ding,
  • Shixiong Mai,
  • Bingqin Yue,
  • Jingyu Chen,
  • Man Huang

摘要

Background

Lung ischemia-reperfusion injury (LIRI) is associated with a variety of postoperative complications and affects patient prognosis. β-Nicotinamide mononucleotide (NMN) has attracted much attention due to its potential role in cellular energy metabolism and antioxidant properties. Exploring the mitigating role of NMN in ischemia-reperfusion injury after lung transplantation is crucial for improving lung transplantation success and patient quality of life.

Methods

A LIRI model was established using the mouse left lung portal clamp method, and the cold ischemia-reperfusion (CI/R) model with BEAS-2B cells in vitro was used to simulate the lung transplantation environment. The protective effect of NMN against lung ischemia-reperfusion injury was analyzed by histopathology, ELISA, immunofluorescence, Western blot and RT-PCR. Combined multi-omics profiling were used to study the mechanisms by which NMN attenuated lung ischemia-reperfusion injury.

Results

NMN significantly attenuated ischemia-reperfusion-induced structural abnormalities, pulmonary edema, inflammatory infiltration and oxidative stress injury in mouse lung tissue. Similarly, NMN attenuated CI/R-induced oxidative stress and inflammatory responses in BEAS-2B cells. Based on multi-omics analysis, we found that NMN ameliorated the apoptosis after ischemia/reperfusion through down-regulation of cleaved Caspase 3, BAX and up-regulation of BCL-2. Moreover, NMN also affected mitochondrial metabolic processes, including promoting mitochondrial oxidative phosphorylation, increasing ATP synthesis, enhancing mitochondrial complex activity, decreasing ROS generation, slowing down the decrease of mitochondrial membrane potential, and inhibiting the opening of the mitochondrial membrane permeability transition pore. Mechanistically, we found that NMN attenuates inflammation and oxidative damage through activation of the SIRT1 and NF-κB signaling pathways, and that SIRT1-specific inhibition of EX527 reversed these protective effects of NMN against inflammation and oxidative damage in vivo and in vitro.

Conclusion

NMN has a protective effect on inflammation and oxidative damage induced by ischemia-reperfusion injury after lung transplantation, and the SIRT1/NF-κB pathway may be involved in one of the mechanisms of the protective effect.