Dexmedetomidine relieves LPS-induced acute lung injury by boosting HIF-1a/ACOD1 driven anti-inflammatory macrophage polarization

  • Genes Immun. 2025 Sep 24. doi: 10.1038/s41435-025-00355-1.
Ning Zhang  #  1 ,  Tangbing Chen  #  2 ,  Yintao Chang  #  3 ,  Mingzhi Cao  1 ,  Huan Wang  1 ,  Chengli Wu  4 ,  Hong Jiang  5
Affiliations
  • 1. Department of Thoracic Surgery, 905th Hospital of People's Liberation Army Navy, Naval Medical University, Shanghai, China.
  • 2. Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • 3. Department of Thoracic Surgery, Changzheng Hospital, Naval Medical University, Shanghai, China.
  • 4. Department of Oncology, 905th Hospital of People's Liberation Army Navy, Naval Medical University, Shanghai, China. [email protected].
  • 5. Department of Thoracic Surgery, 905th Hospital of People's Liberation Army Navy, Naval Medical University, Shanghai, China. [email protected].
  • # Contributed equally.
PMID: 40993330 DOI: 10.1038/s41435-025-00355-1
Abstract

Acute lung injury (ALI) is a common and life-threatening lung disease. This study investigated the mechanism by which dexmedetomidine (Dex) alleviates lipopolysaccharide (LPS)-induced ALI, focusing on its regulation of macrophage Autophagy and polarization. Initially, a mouse model of LPS-induced ALI was pretreated with Dex. Pulmonary function, histopathological changes, Apoptosis, macrophage numbers in bronchoalveolar lavage fluid (BALF), M1/M2 macrophage ratios, iNOS/Arg-1/LC3/p62 fluorescence intensity, and Autophagy flux were assessed. Subsequently, RAW264.7 macrophages were treated with LPS and Dex, transfected with si-ACOD1 or si-HIF-1α, and co-cultured with mouse pulmonary microvessel endothelial cells (MPMVECs). The results showed that Dex relieved Autophagy flux blockage and promoted Autophagy in ALI mice. LPS promoted ACOD1 and HIF-1α levels, and Dex further enhanced their levels to boost macrophage Autophagy and M2 polarization. ACOD1 was transcriptionally regulated by HIF-1α. Collectively, Dex mitigated LPS-induced MPMVEC injury and ALI by enhancing HIF-1α-mediated ACOD1 transcription, thus promoting macrophage Autophagy and M2 polarization.

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