BML-111, a lipoxin receptor agonist, protects haemorrhagic shock-induced acute lung injury in rats.

Abstract

The main pathogenesis of acute lung injury induced by haemorrhagic shock is inflammation. BML-111, a lipoxinA(4)-receptor agonist, promotes acute inflammatory resolution. We sought to elucidate whether BML-111 protects haemorrhagic shock-induced acute lung injury in rats. Thirty two adult male rats were randomized to sham group (sham), haemorrhagic shock/resuscitation (HS), HS plus BML-111 (BML-111), and HS plus BML-111 and BOC-2 (BOC-2). Haemorrhagic shock was induced by blood drawing, and then resuscitation was obtained by infusion of shed blood and two-fold volume saline. Histological findings, as well as assays of neutrophilic infiltration (myeloperoxidase activity, ICAM-1 expression), inflammatory cytokines and pro-inflammatory factor (IκB-α and NF-κB p65) confirmed that haemorrhagic shock induced acute lung injury. BML-111 significantly mitigated acute lung injury induced by haemorrhagic shock. However, BOC-2, an antagonist of the lipoxinA(4)-receptor, partially reversed the protective effect of BML-111 on the haemorrhagic shock-induced the acute lung injury. BML-111 protects haemorrhagic shock-induced acute lung injury in rats.