光气急性染毒对大鼠肝脏的影响

Effects of acute phosgene exposure on liver in rats

目的探讨光气染毒对大鼠肝脏的影响。方法将健康成年雄性SD大鼠随机分为对照组、光气染毒组,每组共30只;动物置于染毒箱内,对照组动物吸入空气5 min,染毒组动物吸入浓度为8.33 mg/L的光气5 min;在染毒后1、3、6、12、24 h,采用质量分数为20%的乌拉坦腹腔注射麻醉后,采集血液样本和肝脏组织,进行血气分析、丙氨酸氨基转移酶(ALT)和门冬氨酸氨基转移酶(AST)检测,在对肝脏组织进行苏木素-伊红(HE)染色后,光镜下观察病理学变化。结果染毒3 h后,大鼠动脉氧分压和氧合指数明显下降,6 h达到最低点,分别为(58.67±8.64)mm Hg(临床呼吸衰竭标准<60 mm Hg)和(202.30±29.80)mm Hg(急性肺损伤诊断标准<300 mm Hg,急性呼吸窘迫综合征诊断标准<200 mm Hg);3 h和6 h时染毒组ALT明显高于对照组(t=6.399,P<0.01;t=4.165,P<0.01),AST在各时间点均有升高(P<0.05)。1 h时染毒组肝脏器系数较对照组升高(t=2.982,P=0.01),在3 h、6 h时达到峰值,明显高于对照组(t=3.780,P<0.01;t=4.633,P<0.01),12 h、24 h时较前略有下降,但与对照组差异仍有统计学意义(t=2.353,P=0.04;t=2.594,P=0.03)。HE染色后可见染毒组肝细胞索间红细胞浸润多见,且越接近中央静脉区越严重,在染毒3 h后达到高峰,之后逐渐缓解,24 h时接近正常。结论光气染毒可以引起肝内淤血、肝质量增加和转氨酶增高,此可能与吸入光气后导致的低氧血症和血液流变学变化及随之发生的氧化应激有关。

Objective To investigate the effect of acute exposure of phosgene on liver of rats.Methods Rats were randomized into 2 groups:control group and ALI caused by acute inhalation of phosgene group,30 rats in each group(6 rats for each time point).The blood samples were taken at 1,3,6,12 and 24 h after phosgene inhalation,then detect the serum levels of alanine aminotransferase(ALT),aspartate amino transferase(AST),respectively;meanwhile,blood gas analysis and pathological examination on liver using haematoxylin andeosin staining were performed as well.Results The results showed that 3 h later after phosgene inhalation,the arterial oxygen partial pressure and oxygenation index were all decreased(P<0.01 vs.control),6 h later after phosgene inhalation,the index reached the lowest point,the arterial oxygen partial pressure[(58.67±8.64)mm Hg]reached the clinical respiratory standard(<60 mm Hg)and the oxygenation index[202.30±29.80)mm Hg]reached the diagnostic standard of acute lung injury and ARDS(<300 mm Hg and<200 mm Hg).The ALT and AST were all increased in phosgene groups.Meanwhile,liver organ coefficient got worse with the time in phosgene group.Hepatic histopathology examination found some blood flow stasis especially near the central venous area of liver.Conclusion The results suggested that phosgene exposure could cause intrahepatic congestion,increase of hepatic weight and rise of transaminases activities,which might be related to hypoxemia,hemorheological changes by phosgene inhalation and following oxidative stress.