淡水淹溺致急性肺损伤兔模型的制备

A rabbit model of acute lung injury induced by freshwater drowning

目的通过向新西兰兔气管内灌注不同剂量淡水,研究淡水淹溺型急性肺损伤动物模型的制备方法。方法健康新西兰兔28只,随机均分为空白对照(C)组及F8组、F10组、F12组(分别灌注8、10、12ml/kg淡水)。观察各组灌注前,灌注即刻(0min),灌注后5、30min和1、2、3h的呼吸频率、心率、平均动脉压(MAP)、动脉血气。于实验终点处死动物,观察肺组织病理学变化,计算肺湿/干重比和微血管通透指数的变化。结果各淡水灌注组在灌注即刻呼吸频率均明显增快,口唇发绀,双肺底闻及少许湿啰音;灌注瞬间心率均有少许加快,但与C组及灌注前比较无统计学意义。F8组和F10组在灌注淡水后MAP变化缓慢,于30min后下降,与灌注前和C组比较均有显著差异(P<0.05);F12组在灌注即刻MAP即出现下降,与灌注前和C组比较均有显著差异(P<0.05)。各灌注组动物均出现低氧血症、低碳酸血症,氧合指数、BE值和渗透压下降,F12组自灌注时即出现氧合指数低于300mmHg并维持1h,与F8、F10组比较更稳定、持久。各灌注组动物的肺组织均可见不同程度的损伤,且肺微血管通透性增加,但仅F12组肺组织湿/干重比增加(P<0.05)。结论不同剂量淡水灌注均可引起不同程度肺损伤,灌注淡水12ml/kg可以成功建立较为稳定的淡水淹溺型急性肺损伤模型。

Objective To reproduce a rabbit model of acute lung injury induced by freshwater drowning by means of introduction of different volume of freshwater into trachea of rabbits. Methods Twenty-eight healthy New Zealand rabbits were randomly assigned to four groups （7 each）; control group and three freshwater drowning groups. For the drowning groups, the animals were given intratracheally 8ml/kg （F8）, 10ml/kg （F10） and 12ml/kg （F12） of freshwater, respectively. For the animals in all the groups, the respiratory rate, heart rate, mean arterial pressure （MAP） and blood gases were observed and analyzed before experiment and at 0min, 5min, 30min, 1h, 2h and 3h after freshwater perfusion. Rabbits were sacrificed at the termination of experiment, and the histopathological changes in lung tissue were observed, the W/D ratio of pulmonary tissue and PMVP were recorded. Results Tachypnea, cyanosis and wet rales in base of lung appeared in the animals of drowning groups immediately after intraduction of water, and the heart rate was increased slightly but no significant difference compared to that in control group. MAP declined slowly at 30min time point in F8 and F10 groups, while immediately at the beginning of perfusion in F12 group. The MAP values in F12 group at every time point after perfusion were different to that before perfusion and that in control group （P〈0. 05）. Hypoxemia, hypoeapnia, declination of oxygenation index, base excess （BE） and osmotic pressure were observed in all the three drowning groups. The low level of oxygenation index （〈300mmHg） appearing in F12 group at the time of perfusion, was maintained for one hour and more persistent and stable compared with F8 and F10 groups. Lung injury and elevated PMVP occurred in all the three drowning groups, but W/D ratio increased only in F12 group （P〈0. 05）. Conclusion Different volumes of freshwater perfusion will induce different degree of injuries to lung. A stable rabbit model of freshwater-induced acute lung injury can be successfully reproduced by perfusion of freshwater in 12ml/kg dosage.