中华眼镜蛇毒口服和静脉注射单次给药对小鼠毒性作用的比较

The acute toxicity of Najanajaatra venom(NNAV)by oral and intravenous administration

目的：比较中华眼镜蛇毒（NNAV）经口灌服、静脉注射两种染毒途径的半数致死量（LD_（50））,观察两种染毒途径小鼠的急性中毒症状,寻找可能发生毒性作用的靶器官。方法：小鼠经口灌服、静脉注射NNAV后,测定半数致死量（LD_（50））。观察14d内小鼠的活动、体征及死亡情况,并对死亡小鼠和存活14d小鼠的主要脏器进行病理组织学检查。结果：小鼠经口灌服、静脉注射NNAV的LD_（50）分别为102.3、0.624mg/kg,95%CI 84.9～123、0.572～0.680mg/kg。NNAV经口灌服小鼠中毒症状出现快,喘息、强直性抽搐、呼吸抑制、心衰很快死亡;急性中毒受损器官主要为肺毛细血管充血,局部肺泡间隔增宽伴少量炎性细胞浸润;肝血管充血。NNAV静脉注射小鼠中毒症状为瘫卧、呼吸功能麻痹,心肺功能衰竭而死亡。急性中毒受损器官主要为肺泡腔内及细支气管内有红细胞,血管壁周围有水肿;肝细胞弥漫性肿大,致肝小叶结构不清,肝细胞肿胀,基质稀疏,有的呈气球样变,肝血窦受压变狭或消失。结论：NNAV口服染毒的毒性剂量明显低于静脉注射,二种染毒途径动物急性中毒器官的受损程度也有所不同;NNAV两种染毒途径存活14d的小鼠其组织病理改变均可恢复。

Objective：To compare the lethal dose 50（LD_（50））of Najanajaatra venom（NNAV）with two routes of drug administration and to explore the target organs of acute toxicity of NNAV,and to observe the acute poisoning symptoms of the mice and organ lesions with oral and intravenous administration of NNAV. Methods： Two different modes of drug administration（oral administration and intravenous injection）were used to determine the LD_（50）.Within 14 of survival time period,the activities,signs and death of the mice were observed.Then,pathology analysis was applied to the main organs of the dead and survival mice.Results：The LD_（50） of NNAV by oral administration and intravenous injection was 102.3 and 0.624mg/kg,and the 95%confidence limit range was 84.9-123.3mg/kg and 572.3-680μg/kg,respectively.The poisoning does by oral administration was 100 times larger than that by intravenous injection,indicating NNAV could be absorbed through gut.Conclusions：The toxicity of NNAV by intravenous administration is larger than that by oral administration.The death caused by acute intoxication is mainly due to respiratory failure.The organ damage caused by acute intoxication mainly occurred in lung and liver and it was more sever by intravenous injection.