2. Academic Validation
  3. Dexmedetomidine alleviates acute lung injury by promoting Tregs differentiation via activation of AMPK/SIRT1 pathway

Dexmedetomidine alleviates acute lung injury by promoting Tregs differentiation via activation of AMPK/SIRT1 pathway

  • Inflammopharmacology. 2022 Dec 19;1-16. doi: 10.1007/s10787-022-01117-5.
Zheng-Tao Zhang 1 2,  Ke Xie 1 2 3,  Ren-Jie Luo 1 2,  Dan-Ying Zhang 1,  Zhi-Wei He 1,  Ke-Feng Li 1 4,  Shi-Hui Lin 1,  Fang Xu 5
Affiliations

Affiliations

  • 1 Department of Critical Care Medicine, The First Affiliated Hospital of Chongqing Medical University, No.1, Youyi Road, Yuzhong District, Chongqing city, 400016, China.
  • 2 The Chongqing Key Laboratory of Translational Medicine in Major Metabolic Diseases, Chongqing city, China.
  • 3 Department of Critical Care Medicine, The Second Affiliated Hospital of Chongqing Medical University, Chongqing city, China.
  • 4 Department of Critical Care Medicine, Fengjie Hospital, A Branch of The Second Affiliated Hospital of Chongqing Medical University, Chongqing city, China.
  • 5 Department of Critical Care Medicine, The First Affiliated Hospital of Chongqing Medical University, No.1, Youyi Road, Yuzhong District, Chongqing city, 400016, China. [email protected].
PMID: 36534240 DOI: 10.1007/s10787-022-01117-5
Abstract

Objectives: To explore the anti-inflammatory effect and the potential mechanism of dexmedetomidine in ARDS/ALI.

Materials and methods: C57BL/6 mice and EL-4 cells were used in this research. The ALI model was established by CLP. The level of inflammatory cytokines in the lung and blood, the severity of lung injury, the expression of Foxp3, and the proportion of Tregs were detected before and after dexmedetomidine treatment. The expression of the AMPK/SIRT1 after dexmedetomidine treatment was detected in vivo and in vitro. After blocking the AMPK/SIRT1 pathway or depleting Tregs in vivo, the level of the inflammatory response, tissue injury, and Tregs differentiation were detected again to clarify the effect of dexmedetomidine.

Results: Dexmedetomidine significantly reduced systemic inflammation and lung injury in CLP mice. Dexmedetomidine enhanced the Foxp3 expression in the lungs and the frequency of Tregs in the spleen. Dexmedetomidine up-regulated the protein expression of p-AMPK and SIRT1 in lungs and EL-4 cells and facilitated the differentiation of naïve CD4+ T cells into Tregs in vitro. Meanwhile, DEX also increased the expression of Helios in Treg cells.

Conclusions: DEX could improve ARDS/ALI by facilitating the differentiation of Tregs from naïve CD4+ T cells via activating the AMPK/SIRT1 pathway.

Keywords

AMP-activated protein kinase; Acute lung injury; Acute respiratory distress syndrome; Dexmedetomidine; Regulatory T cells; Sirtuin1.

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