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缺氧诱导因子1在急性肺损伤中的双重作用：组织特异性机制与治疗调控

Dual Roles of Hypoxia-Inducible Factor 1 in Acute Lung Injury: Tissue-Specific Mechanisms and Therapeutic Modulation.

作者信息

Jia Junjing, Zhang Yingyi, Lu Qianying, Tian Sijia, Zhao Yanmei, Fan Haojun

机构信息

School of Disaster and Emergency Medicine, Tianjin University, Tianjin 300072, China.

Tianjin Key Laboratory of Disaster Medicine Technology, Tianjin 300072, China.

出版信息

Cells. 2025 Jul 16;14(14):1089. doi: 10.3390/cells14141089.

DOI:10.3390/cells14141089
PMID:40710342
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12293812/
Abstract

Acute lung injury (ALI), a life-threatening clinical syndrome with multifactorial origins, is characterized by uncontrolled pulmonary inflammation and disrupted alveolar-capillary barrier integrity, leading to progressive hypoxemia and respiratory failure. In this hypoxic setting, hypoxia-inducible factor (HIF)-1 is activated, acting as a central regulator of the inflammatory response and reparative processes in injured lung tissue during ALI. The role of HIF-1 is distinctly dualistic; it promotes both anti-inflammatory and reparative mechanisms to a certain extent, while potentially exacerbating inflammation, thus having a complex impact on disease progression. We explore the latest understanding of the role of hypoxia/HIF-mediated inflammatory and reparative pathways in ALI and consider the potential therapeutic applications of drugs targeting these pathways for the development of innovative treatment strategies. Therefore, this review aims to guide future research and clinical applications by emphasizing HIF-1 as a key therapeutic target for ALI.

摘要

急性肺损伤（ALI）是一种起源多因素的危及生命的临床综合征，其特征为不受控制的肺部炎症和肺泡-毛细血管屏障完整性破坏，导致进行性低氧血症和呼吸衰竭。在这种缺氧环境中，缺氧诱导因子（HIF）-1被激活，在ALI期间作为受损肺组织中炎症反应和修复过程的核心调节因子发挥作用。HIF-1的作用具有明显的双重性；它在一定程度上促进抗炎和修复机制，同时可能加剧炎症，因此对疾病进展产生复杂影响。我们探讨了对缺氧/HIF介导的炎症和修复途径在ALI中的作用的最新认识，并考虑了针对这些途径的药物在开发创新治疗策略方面的潜在治疗应用。因此，本综述旨在通过强调HIF-1作为ALI的关键治疗靶点来指导未来的研究和临床应用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3ad1/12293812/37b4d8f00c32/cells-14-01089-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3ad1/12293812/6e278129b911/cells-14-01089-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3ad1/12293812/91ca8f03756d/cells-14-01089-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3ad1/12293812/1af422973b81/cells-14-01089-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3ad1/12293812/bbc86a02c27a/cells-14-01089-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3ad1/12293812/37b4d8f00c32/cells-14-01089-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3ad1/12293812/6e278129b911/cells-14-01089-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3ad1/12293812/91ca8f03756d/cells-14-01089-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3ad1/12293812/1af422973b81/cells-14-01089-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3ad1/12293812/bbc86a02c27a/cells-14-01089-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3ad1/12293812/37b4d8f00c32/cells-14-01089-g005.jpg

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本文引用的文献

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Int J Mol Sci. 2024 Oct 5;25(19):10734. doi: 10.3390/ijms251910734.
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Araloside A alleviates sepsis-induced acute lung injury via PHD2/HIF-1α in macrophages.阿瑞洛苷 A 通过巨噬细胞中的 PHD2/HIF-1α 缓解脓毒症引起的急性肺损伤。
Phytomedicine. 2024 Dec;135:156089. doi: 10.1016/j.phymed.2024.156089. Epub 2024 Sep 20.
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Esketamine alleviates ferroptosis-mediated acute lung injury by modulating the HIF-1α/HO-1 pathway.
依沙佐米通过调节 HIF-1α/HO-1 通路缓解铁死亡介导的急性肺损伤。
Int Immunopharmacol. 2024 Dec 5;142(Pt A):113065. doi: 10.1016/j.intimp.2024.113065. Epub 2024 Sep 6.
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Xanthoxylin Attenuates Lipopolysaccharide-Induced Lung Injury through Modulation of Akt/HIF-1α/NF-κB and Nrf2 Pathways.黄皮酰胺通过调节 Akt/HIF-1α/NF-κB 和 Nrf2 通路减轻脂多糖诱导的肺损伤。
Int J Mol Sci. 2024 Aug 10;25(16):8742. doi: 10.3390/ijms25168742.
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