Protective effects of α_1 -antitrypsin on acute lung injury in rabbits induced by endotoxin  

作　　者：揭志军 蔡映云 杨文兰 金美玲 朱威 祝慈芳 

机构地区：[1]Department of Pulraonology, Zhongshan Hospital, Medical Center of Fudan University, Shanghai 200032, China [2]Department of Pulmonology, Zhongshan Hospital, Medical Center of Fudan University, Shanghai 200032, China [3]Shanghai Biological Production Research Institute, Shanghai 200052, China

出　　处：《Chinese Medical Journal》2003年第11期1678-1682,共5页中华医学杂志（英文版）

基　　金：the Scientific Foundation of the Ministry of Health (No: 98-1-150)

摘　　要：Objective To investigate whether pretreatment with α1,-antitrypsin (AAT) can attenuate acute lung injury (ALI) in rabbits induced with endotoxin.Methods Thirty-two healthy adult New Zealand rabbits were anaesthetized, tracheotomized and mechanically ventilated. They were then randomly divided into four groups (n =8): (1) Infusion of Escherichia coli endotoxin [ Lipopolysaccharide (LPS) 500μg/kg ] without AAT (Group LPS). (2) Infusion of AAT 120 mg/kg at 15 minutes after LPS (Group LAV). (3) Infusion of AAT 120 mg/kg without endotoxin (Group AAT). (4) Infusion of saline 4 ml/kg as control (Group NS). Arterial blood gases, peripheral leukocyte counts and airway pressure were recorded every hour for eight hours. Physiologic intrapulmonary shunting (Qs/Qt) was measured every four hours. After eight hours, blood samples were collected for measurement of plasma concentration and activity of AAT. Then, the animals were sacrificed, and bronchoalveolar lavage fluid (BALF) was collected for measurement of concentrations of total protein (TP), interleukin-8 (IL-8), tumor necrosis factor (TNFa, the activities of NE and AAT, total phospholipids (TPL) and disaturated phosphatidylcholine (DSPC). In addition, the wet-to-dry lung weight ratio (W/D) was measured.Results The infusion of endotoxin induced decreases in arterial oxygen pressure (PaO2), peripheral leukocyte counts, total respiratory compliance (TLC) and the increases in peak pressure (Ppeak), Qs/ Qt compared with the baseline values ( P < 0. 05). The increased plasma concentration but reduced activity of AAT was also found in contrast to that in Group NS (P<0. 05). In the BALF, the activity of AAT, TPL, DSPC/TPL were lower than those in Group NS (P<0. 05), but the concentrations of albumin, IL-8, TNFα, the activity of NE and the ratio of W/D were higher than those in Group NS (P <0. 05). The pretreatment of AAT attenuated the deterioration of oxygenation, the reduction of compliance and the deterioration of other physiological and biochemical parameters mentioned abObjective To investigate whether pretreatment with α1,-antitrypsin (AAT) can attenuate acute lung injury (ALI) in rabbits induced with endotoxin.Methods Thirty-two healthy adult New Zealand rabbits were anaesthetized, tracheotomized and mechanically ventilated. They were then randomly divided into four groups (n =8): (1) Infusion of Escherichia coli endotoxin [ Lipopolysaccharide (LPS) 500μg/kg ] without AAT (Group LPS). (2) Infusion of AAT 120 mg/kg at 15 minutes after LPS (Group LAV). (3) Infusion of AAT 120 mg/kg without endotoxin (Group AAT). (4) Infusion of saline 4 ml/kg as control (Group NS). Arterial blood gases, peripheral leukocyte counts and airway pressure were recorded every hour for eight hours. Physiologic intrapulmonary shunting (Qs/Qt) was measured every four hours. After eight hours, blood samples were collected for measurement of plasma concentration and activity of AAT. Then, the animals were sacrificed, and bronchoalveolar lavage fluid (BALF) was collected for measurement of concentrations of total protein (TP), interleukin-8 (IL-8), tumor necrosis factor (TNFa, the activities of NE and AAT, total phospholipids (TPL) and disaturated phosphatidylcholine (DSPC). In addition, the wet-to-dry lung weight ratio (W/D) was measured.Results The infusion of endotoxin induced decreases in arterial oxygen pressure (PaO2), peripheral leukocyte counts, total respiratory compliance (TLC) and the increases in peak pressure (Ppeak), Qs/ Qt compared with the baseline values ( P < 0. 05). The increased plasma concentration but reduced activity of AAT was also found in contrast to that in Group NS (P<0. 05). In the BALF, the activity of AAT, TPL, DSPC/TPL were lower than those in Group NS (P<0. 05), but the concentrations of albumin, IL-8, TNFα, the activity of NE and the ratio of W/D were higher than those in Group NS (P <0. 05). The pretreatment of AAT attenuated the deterioration of oxygenation, the reduction of compliance and the deterioration of other physiological and biochemical parameters mentioned ab

关 键 词：acute lung injury ·α1-antitrypsin neutrophil elastase ·rabbits ENDOTOXIN 

分 类 号：R563[医药卫生—呼吸系统]