α1-ANTITRYPSIN ATTENUATES ENDOTOXIN-INDUCED ACUTE LUNG INJURY IN RABBITS

Objective To investigα1e whether pretreα1ment with α1-AT can α1tenuα1e acute lung injury (ALl) in rabbits indwc.ed with endotoxin . Methods Thirty-two New Zealand rabbits were randomly assigned to four groups( n = 8 ) : 1. Infusion of endotoxin (Lipopolysaccharide, LPS 500μg/kg) without α1-AT (group LPS). 2. Infusion α1-AT 120mg/ kg at 15min before challenge with LPS ( group LAV). 3. Infusion of α1-AT 120mg / kg( group AAT ) . 4 Infusion of saline 4ml / kg as control (group NS ) . Arterial blood gases, peripheral leukocyte counts and airway pressure were recorded every lb. Physiologic intrapuimonary shunting ( Qs / Qt ) was measured every 4h. After 8h the bloods were collected for measurement of plasma concentration and activity of α1 -AT. Then bronchoaiveolar iavage fluid (BALF) was collected for measurement of concentrations of total pro-tein ( TP ), interleukin-8 ( IL-8 ), tumor necrosis factor ( TNF-α), the activities of elastase-like and α1-AT, total phospholipids( TPL ) and disaturated phosphatidylcholine ( DSPC ). In addition, the wet-to-dry lung weight ratio (W/D) was measured. Reaults After infusion of endotoxin, it was observed that Pa02 , peripheral lueko-cyte counts, total respiratory compliance progressively decreased and Ppcak and Qs / Qt increased comparing with the baseline values. In contrast to group NS, the increased plasma concentration but reduced activity of α1-AT was found in group LPS. In the BALF, the activity of α1-AT, TPL, DSPC/TPL were lower, but the concentra-tions of albumin, IL-8, TNF-α,and the activity of NE were higher. The ratio of W/ D also increased. The pre-treatment of α1-AT attenuated the deterioration of oxygenation, the reduction of compliance and the deteriora-tion of other physiological, biochemical parameters mentioned above. Conelusion Pretreatment with α1-ATcould attenuate endotoxin-induced lung injury in rabbits. Those beneficial effects of α1-AT might be due in part to the inhibitory effect on neutrophil elastase.