Dexmedetomidine attenuates lipopolysaccharide induced acute lung injury by targeting NLRP3 via miR-381

J Biochem Mol Toxicol. 2018 Nov;32(11):e22211. doi: 10.1002/jbt.22211. Epub 2018 Aug 13.

Abstract

Dexmedetomidine (Dex) is an agonist of α2-adrenergic receptors, and it is used as an anxiety reducing, sedative, and pain medication in clinical. Studies have shown that dexmedetomidine protects against lipopolysaccharide (LPS)-induced acute lung injury; however, the underlying mechanism is still unclear. To investigate, an acute lung injury mouse model was induced by intraperitoneal injection of LPS. Histopathological changes were determined by hematoxylin and eosin staining. Enzyme-linked immunosorbent assay was used to detect cytokines in serum. microRNA expression levels were detected by quantitative reverse transcription polymerase chain reaction. Protein levels were detected by western blot. Dex treatment significantly attenuated lung injury and inhibited the expression levels of the inflammation factors via reducing the level of NACHT, LRR, and PYD domains-containing protein 3 (NLRP3) and autocleavage of caspase-1. Moreover, mmu-miR-381, which targets the mRNA of NLRP3, was upregulated after Dex treatment. Dex attenuates LPS-induced acute lung injury via miR-381-targeted NLRP3.

Keywords: NLRP3; acute lung injury; dexmedetomidine (Dex); lipopolysaccharide (LPS); mmu-miR-381.

MeSH terms

  • Acute Lung Injury / chemically induced
  • Acute Lung Injury / metabolism
  • Acute Lung Injury / pathology
  • Acute Lung Injury / prevention & control*
  • Adrenergic alpha-2 Receptor Agonists / therapeutic use*
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use
  • Caspase 1 / metabolism
  • Cytokines / blood
  • Dexamethasone / therapeutic use
  • Dexmedetomidine / therapeutic use*
  • Gene Expression Regulation / drug effects
  • Lipopolysaccharides / toxicity
  • Lung / drug effects*
  • Lung / immunology
  • Lung / metabolism
  • Lung / pathology
  • Male
  • Mice, Inbred C57BL
  • MicroRNAs / agonists*
  • MicroRNAs / metabolism
  • NLR Family, Pyrin Domain-Containing 3 Protein / antagonists & inhibitors*
  • NLR Family, Pyrin Domain-Containing 3 Protein / genetics
  • NLR Family, Pyrin Domain-Containing 3 Protein / metabolism
  • Protective Agents / therapeutic use
  • Proteolysis / drug effects
  • Pulmonary Edema / prevention & control
  • RNA Interference / drug effects*
  • Random Allocation

Substances

  • Adrenergic alpha-2 Receptor Agonists
  • Anti-Inflammatory Agents, Non-Steroidal
  • Cytokines
  • Lipopolysaccharides
  • MIRN381 microRNA, rat
  • MicroRNAs
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Nlrp3 protein, rat
  • Protective Agents
  • Dexmedetomidine
  • Dexamethasone
  • Caspase 1