Ac2-26 ameliorates lung ischemia-reperfusion injury via the eNOS pathway

Biomed Pharmacother. 2019 Sep:117:109194. doi: 10.1016/j.biopha.2019.109194. Epub 2019 Jul 4.

Abstract

Background: Lung ischemia-reperfusion injury (LIRI) is a major complication after lung transplantation. Annexin A1 (AnxA1) ameliorates inflammation in various injured organs. This study aimed to determine the effects and mechanism of AnxA1 on LIRI after lung transplantation.

Methods: Thirty-two rats were randomized into sham, saline, Ac2-26 and Ac2-26/L groups. Rats in the saline, Ac2-26 and Ac2-26/L groups underwent left lung transplantation and received saline, Ac2-26, and Ac2-26/L-NIO, respectively. After 24 h of reperfusion, serum and transplanted lung tissues were examined.

Results: The partial pressure of oxygen (PaO2) was increased in the Ac2-26 group compared to that in the saline group but was decreased by L-NIO treatment. In the Ac2-26 group, the wet-to-dry (W/D) weight ratios, total protein concentrations, proinflammatory factors and inducible nitric oxide synthase levels were notably decreased, but the concentrations of anti-inflammatory factors and endothelial nitric oxide synthase levels were significantly increased. Ac2-26 attenuated histological injury and cell apoptosis, and this improvement was reversed by L-NIO.

Conclusions: Ac2-26 reduced LIRI and improved alveoli-capillary permeability by inhibiting oxygen stress, inflammation and apoptosis. The protective effect of Ac2-26 on LIRI largely depended on the endothelial nitric oxide synthase pathway.

Keywords: Ac2-26; Annexin A1; Ischemia/reperfusion injury; Lung; Transplantation.

MeSH terms

  • Animals
  • Annexin A1 / metabolism
  • Annexin A1 / pharmacology*
  • Anti-Inflammatory Agents / pharmacology
  • Apoptosis / drug effects
  • Inflammation / metabolism
  • Lung / drug effects*
  • Lung / metabolism*
  • Lung Injury / metabolism*
  • Male
  • Nitric Oxide Synthase Type II / metabolism
  • Nitric Oxide Synthase Type III / metabolism
  • Peptides / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Reperfusion Injury / metabolism*

Substances

  • Annexin A1
  • Anti-Inflammatory Agents
  • Peptides
  • annexin A1 peptide (2-26)
  • Nitric Oxide Synthase Type II
  • Nitric Oxide Synthase Type III