Dexmedetomidine alleviates acute lung injury in mice by regulating Toll-like receptor 4/aconitate decarboxylase 1 immune metabolism coupling in macrophages: an experimental study

Li Kefeng; Xu Fang

doi:10.13406/j.cnki.cyxb.003694

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Dexmedetomidine alleviates acute lung injury in mice by regulating Toll-like receptor 4/aconitate decarboxylase 1 immune metabolism coupling in macrophages: an experimental study

Basic research | 更新时间：2025-10-23

- Dexmedetomidine alleviates acute lung injury in mice by regulating Toll-like receptor 4/aconitate decarboxylase 1 immune metabolism coupling in macrophages: an experimental study
- Journal of Chongqing Medical University Vol. 50, Issue 1, Pages: 65-71(2025)
- 作者机构：
  
  重庆医科大学附属第一医院急诊与重症医学科，重庆 400016
- 作者简介：
- 基金信息：
- DOI：10.13406/j.cnki.cyxb.003694
  CLC： R56
- Received：14 May 2024，
  
  Revised：2024-05-21，
  
  Accepted：03 June 2024，
  
  Published：28 January 2025
- 稿件说明：
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李克锋,徐昉.右美托咪定调控巨噬细胞TLR4/ACOD1免疫代谢偶联减轻小鼠急性肺损伤实验研究[J].重庆医科大学学报,2025,50(1):65-71.

Li Kefeng,Xu Fang.Dexmedetomidine alleviates acute lung injury in mice by regulating Toll-like receptor 4/aconitate decarboxylase 1 immune metabolism coupling in macrophages: an experimental study[J].Journal of Chongqing Medical University,2025,50(1):65-71.
李克锋,徐昉.右美托咪定调控巨噬细胞TLR4/ACOD1免疫代谢偶联减轻小鼠急性肺损伤实验研究[J].重庆医科大学学报,2025,50(1):65-71. DOI： 10.13406/j.cnki.cyxb.003694.

Li Kefeng,Xu Fang.Dexmedetomidine alleviates acute lung injury in mice by regulating Toll-like receptor 4/aconitate decarboxylase 1 immune metabolism coupling in macrophages: an experimental study[J].Journal of Chongqing Medical University,2025,50(1):65-71. DOI： 10.13406/j.cnki.cyxb.003694.

摘要

目的

探究右美托咪定（Dexmedetomidine，DEX）调控巨噬细胞Toll样受体-4（toll-like receptors-4，TLR4）/乌头酸脱羧酶（aconitate decarboxylase 1，ACOD1）免疫代谢偶联对小鼠肺损伤的影响。

方法

将RAW264.7细胞分为Control、LPS、LPS+DEX 3组，应用Western blot、ELISA实验检测TLR4、ACOD1与促炎细胞因子蛋白表达。将C57 BL/6小鼠分为Control、盲肠结扎穿刺术（cecal ligation and puncture，CLP）、CLP+DEX 3组，实验探究小鼠7 d生存率、肺损伤情况，同时检测肺组织中TLR4、ACOD1表达，以及与肺泡巨噬细胞、外周血中促炎因子蛋白表达情况。随后，在

Acod1

全身性敲除小鼠（

Acod1

-/-

）中检测CLP+DEX治疗后肺损伤情况与野生型（wild type，WT）小鼠CLP+DEX治疗后的变化。最后提取WT与

Acod1

-/-

小鼠骨髓来源巨噬细胞（bone marrow-derived macrophages，BMDM），检测巨噬细胞iNOS表达情况。

结果

LPS刺激RAW264.7后，TLR4、诱导型一氧化氮合酶（inducible nitric oxide synthase，iNOS）、肿瘤坏死因子-α（tumor necrosis factor，TNF-α）与白细胞介素（interleukin，IL）-6蛋白表达升高，DEX治疗后降低。体内实验中，DEX治疗降低了CLP诱导的ARDS/ALI模型小鼠7 d死亡率、弥漫性肺泡损伤、肺水肿以及外周血中促炎细胞因子TNF-α与IL-6的表达，还降低了肺组织与肺泡巨噬细胞中iNOS的表达。DEX也降低了CLP小鼠肺组织内TLR4的表达。而

Acod1

基因的敲除逆转了DEX的治疗效果，使肺损伤加重，使BMDM细胞表达iNOS增强。

结论

右美托咪定可调控巨噬细胞TLR4/ACOD1免疫代谢偶联，降低LPS刺激后的巨噬细胞炎症因子释放，同时减轻小鼠急性肺损伤。

Abstract

Objective

To investigate the effect of dexmedetomidine（DEX） on lung injury in mice by regulating Toll-like receptor-4 （TLR4）/aconitate decarboxylase 1（ACOD1） immune metabolism coupling in macrophages.

Methods

RAW264.7 cells were divided into control group，LPS group，and LPS+DEX group，and Western blot and ELISA were used to measure the expression levels of TLR4

，ACOD1，and proinflammatory cytokines. C57 BL/6 mice were divided into control group，cecal ligation and puncture（CLP） group，and CLP+DEX group，and experiments were conducted to observe the 7-day survival rate and lung injury of mice，as well as the expression levels of TLR4 and ACOD1 in lung tissue and the expression levels of proinflammatory cytokines in alveolar macrophages and peripheral blood. Subsequently，Acod1 systemic knockout（

Acod1

-/-

） mice were used to observe the condition of lung injury after CLP+DEX treatment and the changes after CLP+DEX treatment in wild-type（WT） mice. Finally，bone marrow-derived macrophages（BMDMs） were extracted from WT and

Acod1

-/-

mice to measure the expression level of inducible nitric oxide synthase（iNOS） in macrophages.

Results

After LPS stimulation of RAW264.7 cells，there were increases in the expression levels of TLR4，iNOS，tumor necrosis factor-α（TNF-α），and interleukin-6（IL-6），which were reduced after DEX treatment.

In vivo

experiments showed that DEX treatment reduced the 7-day mortality rate，diffuse alveolar injury，pulmonary edema，and the expression levels of the proinflammatory cytokines TNF-α and IL-6 in peripheral blood in mice with CLP-induced acute respiratory distress syndrome/acute lung injury，and it also reduced the expression level of iNOS in lung tissue and alveolar macrophages. In addition，DEX reduced the expression level of TLR4 in the lung tissue of CLP mice. Knockout of the

Acod1

gene reversed the therapeutic effect of DEX，aggravated lung injury，and increased the expression of iNOS in BMDMs.

Conclusion

Dexmedetomidine can regulate TLR4/ACOD1 immune metabolism coupling in macrophages，reduce the release of inflammatory cytokines in macrophages after LPS stimulation，and alleviate acute lung injury in mice.

关键词

Keywords

references

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