Dopamine D1 receptor agonist A-68930 inhibits NLRP3 inflammasome activation and protects rats from spinal cord injury-induced acute lung injury

Spinal Cord. 2016 Nov;54(11):951-956. doi: 10.1038/sc.2016.52. Epub 2016 Apr 12.

Abstract

Study design: Randomized experimental study.

Objectives: The study aimed to investigate the therapeutic efficacy and molecular mechanisms of A-68930 in a rat model of spinal cord injury (SCI)-induced acute lung injury (ALI).

Setting: China.

Methods: The influences of A-68930 on the pulmonary edema, histological changes, proinflammatory cytokines levels, myeloperoxidase (MPO) activity and NLRP3 inflammasome protein expression were estimated.

Results: SCI significantly promoted NLRP3 inflammasome activation, increased proinflammatory cytokine productions and MPO activity, and induced pulmonary edema and tissue damage in the SCI group as compared with the control group. A-68930 administration significantly inhibited NLRP3 inflammasome activation and reduced inflammatory cytokines levels and MPO activity. Moreover, A-68930 administration attenuated pulmonary edema and histopathology.

Conclusion: Our experimental findings indicated that A-68930 exhibited a protective effect on SCI-induced ALI by the alleviations of inflammatory response with the inhibition NLRP3 inflammasome activation 72 h post injury. The present study indicated that A-68930 could be a potentially efficient therapeutic strategy for the treatment of SCI-induced ALI.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Acute Lung Injury / drug therapy*
  • Acute Lung Injury / etiology*
  • Animals
  • Capillary Permeability / drug effects
  • Chromans / therapeutic use*
  • Cytokines / metabolism
  • Disease Models, Animal
  • Dopamine Agonists / therapeutic use*
  • Dose-Response Relationship, Drug
  • Female
  • Gene Expression Regulation / drug effects
  • NLR Family, Pyrin Domain-Containing 3 Protein / metabolism*
  • Organ Size / drug effects
  • Peroxidase / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Spinal Cord Injuries / complications*
  • Time Factors

Substances

  • Chromans
  • Cytokines
  • Dopamine Agonists
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Nlrp3 protein, rat
  • A 68930
  • Peroxidase