不同浓时积光气致大鼠急性死亡及氧化损伤作用

Acute death and oxidative damage induced by acute phosgene inhalation of different concentration-time (Ct) in rats

目的观察不同浓时积(concentration×time,Ct)光气致大鼠急性死亡和氧化损伤的作用。方法雄性SD大鼠60只随机分为对照组和5个光气染毒组,Ct分别为3ml×3min,15ml×1min,7.5ml×2min,5ml×3min及10ml×3min(30ml/min)。染毒后观察24h,计算病死(比)率。免疫组化法测定染毒后24h的肝脏核转录因子(NF-κB)的表达。以无动物死亡组作为氧化损伤观察组,染毒后24h测定肺脏湿干比、血清和肝脏丙二醛(MDA)及超氧化物歧化酶(SOD)。结果(1)病死比:对照组(0/10)、3×3组(0/10)、15×1组(0/10)、7.5×2组(4/10)、5×3组(4/10)、10×3组(10/10);(2)NF-κB:除对照组外,染毒组均有表达,15×1组最明显;(3)氧化损伤:对照组、3×3组和15×1组无动物死亡,作为氧化损伤观察组。各组肺湿干比与对照组差异无统计学意义(P>0.05);15×1组肝脏MDA、肝脏和血清SOD较对照组升高(P<0.05);3×3组各指标与对照组比较差异无统计学意义(P>0.05)。结论Ct值相同时,染毒时间越长,中毒越重,表明光气吸入导致动物死亡的过程中,染毒时间的作用大于染毒浓度;而非致死剂量的光气吸入造成的炎性反应和氧化损伤则与染毒浓度密切相关。

Objective To investigate acute death and oxidative damage of rat induced by acute phosgene inhalation of different concentration-time（Ct）.Methods Sixty male SD rats were randomly divided into six groups：one control group and five phosgene exposure groups of different Ct（unit：ml·min）of 3×3,15×1,7.5×2,5×3 and 10×3,respectively.After being exposed to phosgene for 24 hours,the fatality rate of each group was calculated,and the expression of nuclear factor（NF-κB）in the liver was detected.The control group and all rats survival groups after exposure to phosgene were defined as the oxidative damage observation groups.The lung wet/dry weight ratio,the content of malondialdehyde（MDA）and the activity of superoxide dismutase（SOD）in the serum and liver were examined.Results The fatality rate was 0/10 in control group,3×3 group and 15×1 group,and 4/10 in 7.5×2 group and 5×3 group,and 10/10 in 10×3 group,respectively.NF-κB was expressed in all groups but the control group,and was most obvious in 15×1 group.The control group,3×3 group and 15×1 group were elected as the oxidative stress observation groups.The lung wet/dry weight ratio of 3？ml×3？min group and 15×1 group showed no difference compared with the control group（P〉0.05）;The content of MDA in liver tissue,the activity of SOD in liver tissue and blood serum of 15×1 group were much higher than that of control group（P〈0.05）.Neither the MDAn or SOD of 3×3 group showed difference compared with control group（P〉0.05）.Conclusion When the Ct was same,the intoxation of phosgene positively correlated with the exposure time,indicating that in the process of acute death induced by phosgene inhalation,the contribution of exposure time was more fatal than that of exposure concentration;In nonlethal condition,the oxidative damage and inflammatory reaction induced by phosgene were closely related to the phosgene＇s concentration.