光气急性中毒的剂量-反应关系与肺水肿动物模型的建立

The dose-response relationship of acute phosgene poisoning and animal model establishment of pulmonary edema

目的明确光气急性中毒的剂量-反应关系与其半数致死浓度(LC50),建立光气中毒肺水肿动物模型,为进一步研究光气损伤机制及防治手段奠定基础。方法小鼠按体重随机分为6组,每组10只,雌雄各半,分别按3.7、4.3、4.7、5.2、5.7、6.3ml给予40%三光气(BTC);大鼠按2.00、3.03、4.58、6.93、10.50ml分别给予BTC,动态染毒3min。随即连续7d观察其进食、活动及死亡情况。应用改良寇氏法计算小鼠、大鼠光气染毒的LC50。小鼠染毒后4h,肺脏右叶称量湿重,放入75℃烤箱烘烤24h,称量肺脏干重,计算肺脏湿干比;取肺脏左叶进行常规HE染色,光镜下观察病理学变化。结果小鼠光气中毒的LC50及其95%可信区间为11.97g/m3(9.52～14.42g/m3)。大鼠光气中毒的LC50及其95%可信区间为13.81g/m3(9.16～14.07g/m3)。光气染毒后,小鼠肺湿干比随时间延长呈逐渐上升趋势,2h时显著高于对照组(P<0.05)。结论本实验确定了小鼠、大鼠光气染毒3min的LC50,并依此成功建立了光气中毒肺水肿模型。

Objective To determine dose-response relationship of phosgene poisoning and establish pulmonary edema animal model, so as to provide basis for further study on lung injury and treatment of phosgene. Methods Rats were randomly divided into 6 groups by weight with 5 male and 5 female mices among each group, Mice were dosed by giving 3.7, 4.3, 4.7, 5.2, 5.7, 6.3 ml BTC; and rats were dosed by giving 2.00, 3.03, 4.58, 6.93, 10.50 ml BTC respectively and dynamically exposed to phosgene at 3 min separately. Then their mortality rates and LC40 were respectively calculated by Karber＇s method. Wet/dry lung weight were measured ratio after baked for 24 h at 75 ℃ ; pathological changes were observed with HE dyed. Results The LC50 of phosgene and 95 % CI on mice and rats was 11.97 g/m^3 （9.52-14.42 g/m^3） and 13.81 g/m^3 （9.16-14.07 g/m^3） respectively. The lung wet/ dry weight ratio of poisoning mice was significantly higher than normal mice （P 〈 0.05）. Conclusions The study determined the LC50 of phosgene on mice and rats after 3 rain exposing, and pulmonary edema animal model was established successfully.