α_1-抗胰蛋白酶对急性肺损伤兔蛋白酶和表面活性物质的影响

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

目的 :观察 α1抗胰蛋白酶 ( α1AT)对内毒素致急性肺损伤兔蛋白酶和表面活性物质的影响。方法 :3 2只成年健康新西兰兔在给予定容机械通气基础上随机分成内毒素 ( L PS)组、L AV组 (内毒素 +α1AT)、AT组 ( α1AT)和生理盐水组 ( NS)。稳定 3 0分钟 ,监测每小时动脉血氧分压 ( Pa O2 )、静态总呼吸顺应性 ( TRC) ,4和 8小时分别测定肺内动静脉分流 ( Qs/Qt)。比较 8小时后血浆 α1AT浓度和活性、支气管肺泡灌洗液( BAL F)中总蛋白 ( TP)浓度、弹性蛋白酶 ( NE)样活性、α1AT活性、总磷脂 ( TPL)和饱和磷酯酰胆碱 ( DSPC)含量等指标以及肺重 /干重 ( W/D)。结果 :动物静脉注射 LPS后 Pa O2 下降 ,氧合指数 ( Pa O2 /Fi O2 ) <2 6.7k Pa( 1 k Pa=7.5mm Hg) ,TRC下降 >50 % ,Qs/Qt增加 >2 5%。与 NS组相比 ,血浆 α1AT含量增高但活性下降 ;BAL F中 TP含量和 NE样活性增加 ,α1AT活性、TPL 和 DSPC/TPL下降 ;W/D增加。L AV组与 LPS组相比 ,上述指标的变化明显改善 :Pa O2 和 TRC的下降幅度较 L PS组减小 ,血浆 α1AT含量和活性、BAL F中α1AT活性、TPL和 DSPC%较 L PS组增高 ;Qs/Qt、BAL F中 TP含量、NE样活性和 W/D较 L PS组降低。结论 :预防性静注 α1AT,可提高机体内的抗蛋白酶活性 ,抑制

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.