神经性毒剂塔崩对小鼠胆碱能系统中毒效应研究  

Toxic effect of tabun on the cholinergic system in mice

作　　者：章子男 马嘉嘉 黄静宜 邢欢纯 李尧 王永安 丁日高 杨军 ZHANG Zi-nan;MA Jia-jia;HUANG Jing-yi;XING Huan-chun;LI Yao;WANG Yong-an;DING Ri-gao;YANG Jun(Institute of Pharmacology and Toxicology,Academy of Military Medical Sciences,Academy of Military Sciences,Beijing 100850,China;Troops No.95865 of PLA,Beijing 102200,China;Fuxing Road Outpatient Department of Chinese PLA General Hospital,Beijing 100851,China;Troops No.32292 of PLA,Mudanjiang,Heilongjiang 157000,China)

机构地区：[1]军事科学院军事医学研究院毒物药物研究所,北京100850 [2]解放军95865部队,北京102200 [3]解放军总医院京南医疗区复兴路门诊部,北京100851 [4]解放军32292部队,黑龙江牡丹江157000

出　　处：《军事医学》2022年第7期481-486,共6页Military Medical Sciences

基　　金：北京市科技新星计划(Z191100001119105);国防科技创新专项(1716312ZT00114601)。

摘　　要：目的评价不同剂量神经性毒剂塔崩对小鼠胆碱能系统中毒效应并探索相关规律。方法小鼠颈部皮下注射不同剂量(100、200、350和500μg/kg)塔崩,于注射染毒后10 min,1、4、24、48和72 h记录体重和脑重,计算脏器系数;Ellman法及ELISA法分别测定小鼠中枢及外周血乙酰胆碱酯酶(AChE)活性及含量。结果重度染毒小鼠体重24 h后明显低于其他组别。不同浓度塔崩对血AChE的抑制率在48 h内均有大幅下降趋势,72 h有一定程度回升。在轻度染毒状态下,24 h时血AChE抑制率呈明显上升;中、重度染毒状态下,抑制率在1 h内维持较高水平,随后大幅下降。脑AChE的毒剂抑制状态与血AChE差异较大,在重度染毒状态下,脑AChE抑制率在4 h内有一定上升趋势,并在24 h内维持一个高度抑制状态后大幅下降;在中、轻度染毒状态下,脑AChE抑制率相近,不随染毒剂量改变而出现明显差异,48 h后均呈上升趋势,但仍明显低于重度染毒组。脑、血AChE均在染毒后一定时间段呈上升趋势。结论小鼠在中、轻度染毒状态下,毒剂几乎不会对中枢AChE产生抑制作用,只有高剂量染毒时才有抑制作用,而血AChE抑制率具参考意义,可初步衡量中毒水平。同时提示,须关注染毒后外周滞留的大量毒剂,中毒救治时应采用多次给药方式,最大限度消除毒剂效应。Objective To assess the toxic effects of different doses of nerve agent tabun on the cholinergic system in mice and to explore the related patterns.Methods Mice were subcutaneously injected with different doses of tabun(100,200,350,and 500μg/kg).Body weight and brain weight were recorded at different time points(10 min,1 h,4 h,24 h,48 h,and 72 h),and organ coefficients were calculated.The activity of AChE was determined using the Ellman method.ELISA was used to determine the content of AChE.Results The body weight of severely exposed mice was significantly lower than that of other groups after 24 h.The inhibitory rates of different concentrations of tabun on blood enzymes decreased significantly within 48 h,but increased to some extent at 72 h.The inhibitory rate increased significantly at 24 h after mild exposure.Under moderate and severe exposure,the inhibitory rate of blood enzymes remained at a high level for1 h and then decreased significantly.The inhibitory state of brain enzymes was significantly different from that of blood enzymes.Under severe exposure,the high inhibitory rate of brain enzymes increased within 4 h and decreased significantly after a high inhibitory state was maintained within 24 h.The inhibitory rate of brain enzymes were similar under moderate and mild exposure,but did not vary significantly with the change in exposure doses.After 48 h,the inhibitory rates of brain enzymes in both exposure states trended up,but were still significantly lower than in the severe exposure group.Both brain enzymes and blood enzymes trended up for some time after administration.Conclusion Under mild or moderate poisoning,the toxic agent has little inhibitory effect on central AChE,but has inhibitory effect at a high dose.Therefore,the inhibitory rate of blood AChE is of referential value and can help measure the severity of poisoning.At the same time,experimental results suggest that we need to pay attention to the large amount of poison retained in the peripheral area after exposure.During the treatment of

关 键 词：神经性毒剂 塔崩 乙酰胆碱酯酶抑制剂 乙酰胆碱酯酶 酶活性 

分 类 号：R827.12[医药卫生—临床医学]