Protective effects of lipoxin A4 analogue on rats with acute pancreatitis associated with lung injury

Objective To investigate the protective effects of lipoxin A4 analogue (LXA4)-ME on acute pancreatitis associated with lung injury (APALI).Methods Ninety male SD rats were randomly divided into sham operation group (n =30),AP group (n =30) and LXA4-ME group (n =30).AP was induced by retrograde injection of 5％ sodium taurocholate ( 1 ml/kg) into the pancreatic duct.In LXA4-ME group,LXA4-ME was administered (87.5 μg/kg) intraveneously after the onset of AP. Sham operation group was given normal saline after the sham operation.The rats were sacrificed at 12 and 24 h after induction of pancreatitis.The serum level of amylase was measured.The histological changes of the pancreas and lung were observed.The activities of myeloperoxidase (MPO) and levels of malondialdehyde (MDA) in the lung tissue were determined.The mRNA levels of tumor necrotizing factor (TNF)-α,interleukin (IL) -1β,IL-6,intercelluar adhesion molecules (ICAM)-1,E-selectin in the lung tissue were measured by using reverse transcription-polymerase chain reaction (RT-PCR).Results The pathological scores of the pancreas [ 12 h:(8.8 ± 1.2),24 h:(7.9 ± 1.3) ] and lung [ (12 h:(3.35 ±0.78),24 h:(3.29 ±0.64) were lower in LXA4-ME group than in AP group [t2h:(11.6±1.4),24h:(11.5±0.7) for the pancreas,and 12 h:(5.15 ±0.99),24 h:(5.05 ±0.75) for the lung] (allP＜0.01).The activity of MPO [(18.06±0.69),(19.52 ±0.76) U/g] and the levelofMDA [(1.725±0.201),(1.626 ±0.224)nmol/mg] at 12 and 24 h in the lung tissue in LXA4-ME group was significantly lower than MPO [ (28.40 ±1.30),(29.28 ± 1.65) U/g] and MDA [ (2.412 ±0.279),(2.518 ±0.216) nmol/mg] in AP group.The expression of the cytokine TNF-α,IL-1β,IL-6,ICAM-1,and E-selectin in the lung tissue in LXA4-ME group was lower than that in AP group (all P ＜ 0.01 ).Conclusion The protective effect of LXA4-ME on APALI is associated with the reduction of neutrophil infiltration and oxidative stress levels.The mechanism may be due to the suppression of expression of pro-inflammatory cytokines and cell adhesion molecules. Key words: Pancreatitis; Lung injury; Lipoxin A4; Tumor necrotizing factor-α; Cell adhesion molecule