急性低血容量性休克后低剂量内毒素致早期急性呼吸窘迫综合征动物模型研制

Experimental study of replication of an animal model of early acute respiratory distress syndrome with acute hemorrhagic shock followed by intravenous injection of low dose endotoxin

目的 :模拟制作一种更接近临床早期急性呼吸窘迫综合征 (ARDS)病理生理过程的动物模型。方法 :2 2只新西兰白兔分成 4组 :1低血容量性休克组 (6只 ) :急性失血后休克过程持续 1小时 ,以心排血量 (CO)低于基础 40 %为准 ,回输放出的血并抗休克处理 90分钟后再观察 4小时 ;2内毒素组 (6只 ) :静注内毒素 (L PS)1μg/ kg,再观察 4小时 ;3休克加内毒素组 (6只 ) :急性低血容量性休克恢复 90分钟后再静注 L PS 1μg/ kg;4对照组 (4只 )只接受相同麻醉和手术操作。静脉麻醉后 ,4组动物均置入 3F的导管监测实验过程的血流动力学和 5 F的导管在股动脉 (放血用 )。动物苏醒后分基础期、低血容量性休克期、休克恢复期、静注 L PS 2小时期和静注 L PS4小时期 5个阶段观察 ,实验结束后取肺泡灌洗液测白介素 1β(IL 1β)浓度和右肺干重 /湿重比。结果 :第 1、2、4组的 CO、动脉血氧分压 (Pa O2 )、肺内分流 (Qs/ Qt)在静注 L PS后 4小时期与基础期比较无显著差异 ,而第 3组的 Pa O2 从 (11.2± 1.8) k Pa(1k Pa=7.5 mm Hg)降至 (9.3± 2 .3) k Pa,Qs/ Qt从 1.9%± 0 .5 %升至 2 .3%± 1.5 % ,与其它组比较虽无显著差异但呈下降趋势 ,且血浆 IL 1β在静注 L PS2小时和 4小时后持续升高 ,分别为 (198.9± 5 5 .

Objective:To replicate an animal model of early acute respiratory distress syndrome(ARDS) for the research of the pathophysiological changes of the disease.Methods:22 New Zealand white rabbits were anaesthetized and a 3F intravenous tube and a 5F femoral artery tube were inserted.They were then randomly divided into four groups:①hemorrhagic shock group(group Ⅰ):hypovolemic shock was induced by hemorrhage from femoral artery reducing cardiac output (CO) to 40% of normal level for 60 minutes,then resuscitated with shed blood,and observation was continued for extra 4 hours;②endotoxin group(group Ⅱ):low dose lipopolysaccharide (LPS) was infused (1 μg/kg,iv),and observation was continued for 4 hours;③hemorrhagic shock plus LPS group (group Ⅲ):LPS was infused (1 μg/kg,iv) after hemorrhagic shock and resuscitation;④control group(group Ⅳ).The interleukin1β(IL1β) concentration in bronchoalveolar lavage were assayed,and the right lung drytowet ratio was measured.Results:The levels of CO,PaO 2 and ratio of shunted blood to total perfusion(s/t) were within normal ranges in group Ⅰ,Ⅱ,Ⅳ in the 4 hours of observation period.Although statistical significance was absent,the aforementioned parameters deteriorated in group Ⅲ.The concentration of IL1β in bronchoalveolar lavage was (18 9±10 0) ng/L,which was significantly higher than that of control group ( P <0 05),and the plasma concentration of IL1β maintained at a high level 〔(198 9±55 0)ng/L and (251 0±119 5)ng/L at 2 and 4 hours after LPS infusion〕 and significantly higher than that of control 〔(71 2±12 0)ng/L, P <0 05〕.There was a significant difference in the drytowet ratios of the animals′right lung between shock plus LPS group and control group (0 17±0 02 vs.0 30±0 03, P <0 05).Conclusions:The pathophysiological changes in the lung of animal model of this experiment proved to be in a stage of acute lung injury prior to lung edema caused by inflammation.Hence the animal model is suitable for experimental investigation of ARDS in early stage.