The protective effect of dopamine on ventilator-induced lung injury via the inhibition of NLRP3 inflammasome

Int Immunopharmacol. 2017 Apr:45:68-73. doi: 10.1016/j.intimp.2017.02.002. Epub 2017 Feb 8.

Abstract

Dopamine (DA), a neurotransmitter, was previously shown to have anti-inflammatory effects. However, its role in ventilator-induced lung injury (VILI) has not been explicitly demonstrated. This study aimed to investigate the therapeutic efficacy and molecular mechanisms of dopamine in VILI. Rats were treated with dopamine during mechanical ventilation. Afterwards, the influence of dopamine on histological changes, pulmonary edema, the lung wet/dry (W/D) ratio, myeloperoxidase (MPO) activity, polymorphonuclear(PMN)counts, inflammatory cytokine levels, and NLRP3 inflammasome protein expression were examined. Our results showed that dopamine significantly attenuated lung tissue injury, the lung W/D ratio, MPO activity and neutrophil infiltration. Moreover, it inhibited inflammatory cytokine levels in the Bronchoalveolar lavage fluid (BAL). In addition, dopamine significantly inhibited ventilation-induced NLRP3 activation. Our experimental findings demonstrate that dopamine exerted protective effects in VILI by alleviating the inflammatory response through inhibition of NLRP3 signaling pathways. The present study indicated that dopamine could be a potential effective therapeutic strategy for the treatment of VILI.

Keywords: Acute lung injury; Dopamine; Interleukin; NLRP3 inflammasome.

MeSH terms

  • Animals
  • Cytokines / metabolism
  • Disease Models, Animal
  • Dopamine / therapeutic use*
  • Humans
  • Inflammasomes / metabolism
  • Inflammation / drug therapy*
  • Inflammation Mediators / metabolism
  • Lung / drug effects*
  • Lung / pathology
  • Male
  • NLR Family, Pyrin Domain-Containing 3 Protein / metabolism*
  • Neutrophil Infiltration / drug effects
  • Rats
  • Rats, Wistar
  • Ventilator-Induced Lung Injury / drug therapy*

Substances

  • Cytokines
  • Inflammasomes
  • Inflammation Mediators
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • NLRP3 protein, human
  • Dopamine