The role of proteaseantiprotease imbalance in acute lung injury induced by endotoxin in rabbits

Objective:To assess the role of proteaseantiprotease imbalance in the pathogenesis of acute lung injury(ALI) in rabbits induced by endotoxin.Methods:16 adult healthy New Zealand rabbits were anaesthetized,tracheotomized and mechanically ventilated,then randomly divided into two groups ( n =8):infusion of Escherichia coli endotoxin 〔lipopolysaccharide(LPS)500 μg/kg,group LPS〕and infusion of saline (group NS).PaO 2,peripheral leukocyte count,airway pressure and s/s/t were recorded for 8 hours.The plasma concentration and activity of α 1antitrypsin(α 1AT) were determined.Then all animals were sacrificed and the bronchoalveolar lavage fluid (BALF) was collected for measurement of concentrations of total protein (TP),interleukin8(IL8),tumor necrosis factor(TNFα),total phospholipids(TPL) and desaturated phosphatidylcholine (DSPC),the activities of neutrophil elastase(NE) and α 1AT.The wettodry lung weight ratio (W/D) was measured.Results:After infusion of endotoxin,it was observed that PaO 2,peripheral leukocyte count,total respiratory compliance progressively decreased and P peak and s/t increased compared with the baseline values.In contrast to group NS the increased plasma concentration but reduced activity of α 1t increased compared with the baseline values.In contrast to group NS the increased plasma concentration but reduced activity of α 1AT were found in LPS group.In the BALF,the activities of α 1AT,TPL,DSPC/TPL were lower than those in group NS,but the concentrations of albumin,IL8,TNFα,the activity of NE and the ratio of W/D were higher than those in group NS.Conclusions:The imbalance between proteases and antiproteases might play an important role in the pathogensis of ALI.