The effect of α_1-antitrypsin on elastase and surfactant in acute lung injury in rabbits

Objective:To investigate whether α 1antitrypsin (α 1AT) can inhibit the activity of neutrophil elastase (NE) and attenuate acute lung injury (ALI) induced by endotoxin in rabbits.Methods:Thirtytwo adult healthy New Zealand rabbits were anaesthetized,tracheostomized and mechanically ventilated,then randomly assigned to four groups ( n= 8):①infusion of Escherichia coli endotoxin (lipopolysaccharide,LPS 500 μg/kg ) without α 1AT (group LPS);②infusion endotoxin with α 1AT (group LAV);③infusion of saline with α 1AT (120 mg/kg,group AT);④infusion of saline without α 1AT (group NS).Partial pressure of oxygen in artery (PaO 2) and airway pressure were recorded every hour and s/t was recorded every four hours during mechanical ventilation period (8 hours).After 8 hours,blood samples were collected for the measurement of plasma concentration and activity of α 1AT.Then the animals were sacrificed,bronchoalveolar lavage fluid (BALF) was collected for measurement of concentrations of total protein (TP),the activities of NE and α 1AT,total phospholipids (TPL) and desaturated phosphatidylcholine (DSPC).The wettodry lung weight ratio (W/D) was measured.Results:After infusion of endotoxin,it was observed that PaO 2,total respiratory compliance progressively decreased and P peak and s/t increased compared with the baseline values.The increased plasma concentrations but reduced activity of α 1AT were also found in contrast to group NS.In the BALF the activity of α 1AT,TPL,DSPC/TPL were lower than group NS,but the concentrations of albumin,the activity of NE and the ratio of W/D were higher than group NS.Pretreatment with α 1AT attenuated the deterioration of oxygenation,the reduction of compliance and the deterioration of other physiological,biochemical parameters mentioned above.Conclusions:Pretreatment with α 1AT can attenuate endotoxininduced lung injury in rabbits.These beneficial effects of α 1AT may be due,in part,to the direct inhibitory effect on neutrophil elastase,in addition to reduction in the destruction of surfactant.