兔下肢挤压伤解除后肺损伤机制及对策

Mechanism and countermeasures of pulmonary damage after "super" crush injury in rabbit lower extremities

目的建立重大自然灾害所引起的超大重量、超长时间的"超级"挤压伤动物模型,研究"超级"挤压伤后肺损伤机制,探讨内皮素(ET)-1受体拮抗剂(波生坦)的治疗作用。方法对新西兰大白兔双下肢臀部以下部位予以35 kg重物,挤压7 d,建立兔下肢挤压伤动物模型。随机分为治疗组(在解除挤压前10 min,于耳缘静脉注射波生坦0.2 mg/kg)、对照组(给予等量0.9%氯化钠溶液)。观察解除挤压后的兔死亡率,测定肺顺应性及肺通气阻力变化,以及血浆及支气管肺泡灌洗液(BALF)中ET-1水平。结果以对照组和治疗组解除压迫后1 h内的死亡率均为2/12,所有兔肺动脉标本均未发现肺主干动脉栓塞的发生,可见不同程度的肺出血、肺水肿等病理变化。对照组解除挤压前的肺顺应性及肺通气阻力均与正常组(2只正常兔)的差异有统计学意义(P值均<0.01)。对照组解除挤压后1 h内及解除挤压后1 h后的肺顺应性及肺通气阻力与解除挤压前的差异均无统计学意义(P值均>0.05),治疗组与对照组间在各时间点的肺顺应性及肺通气阻力的差异均无统计学意义(P值均>0.05)。对照组挤压释放前5 min的血浆ET-1水平及挤压释放后1 h的BALF中ET-1水平均与正常组的差异有统计学意义(P值均<0.01)。对照组挤压释放后5 min及挤压释放后1 h的血浆ET-1水平与挤压释放前5 min的差异均无统计学意义(P值均>0.05)。治疗组与对照组在各时间点的血浆ET-1水平及BALF中ET-1水平的差异均无统计学意义(P值均>0.05)。结论本实验建立的兔"超级"挤压伤动物模型,挤压伤后肺通气阻力与血浆ET-1水平间可能存在相关性,但解除压迫不会对兔肺通气阻力和肺顺应性,以及血浆和BALF中ET-1水平产生显著影响。ET-1受体拮抗剂波生坦并不能在短时间内有效改善兔肺功能,降低死亡率。

Objective To establish an animal model of ＂super＂ crush injury caused by natural hazard, to study the mechanism of lung damage after the injury, and to explore the effect of endothelin （ET） for the treatments of the super crush injury. Methods Overweight and ultra-long time oppression was applied on the lower extremities of rabbits to model a super crush injury. Mortality of the rabbits was recorded after crush release. Lung compliance, airway resistance and ET-1 in plasma and bronchoalveolar lavage fluid （BALF） were detected. ET-1 antagonist （Bosentan） and 0.9% sodium chloride solution were injected into the models of the treating group and the control group, respectively. The mortality, ET-1 concentration in plasma and BALF and lung ventilation function were compared between different groups. Results The rabbits were crushed under a 35 kg object for 7 d. The death rate was 2/12 in one hour after pressure release. No arterial embolism happened in the lung main arteries. Pulmonary hemorrhage and edema were found. There were significant differences in terms of lung compliance and airway resistance between control group and normal group before pressure release （P〈0.01）. Lung compliance and airway resistance within one hour and at one hour after crush release were not significantly different from that before crush release in the control group （P〉 0. 05） or in the treatment group （P 〉 0. 05）. Plasma ET-1concentrations 5 min before release and in BALF in 1 h after crush release were significantly different from those in normal group （P〈0.01）. ET-1 concentrations 5 m in and 1 h after crush release were not significantly different from that 5 min before crush release （P〉0.05）. ET-1 concentrations and BALF in the control group were not significantly different from those in the treatment group （P〉0.05）. Conc＇lusion There may be a correlation between lung airway resistance and serum ET-1. But the release from crush injury can not significantly impact lung airway resistance, lung compliance, and the ET-1 concentrations in the plasma and BALF. Bosentan （Ro24720203）, a ET-1 antagonist, can not improve lung function in a short period of time and reduce mortality in rabbit.