VX染毒小鼠乙酰胆碱酯酶活性和含量与作用时间的相互关系  

Relationship between acetylcholinesterase activity and content and action time of mice exposed to VX

作　　者：黄静宜 章子男 李尧 邢欢纯[1] 王琦 王永安[1] 杨军 HUANG Jing-yi;ZHANG Zi-nan;LI Yao;XING Huan-chun;WANG Qi;WANG Yong-an;YANG Jun(State Key Laboratory of Highly Toxic Substances for Anti-Drug Research,Institute of Pharmacology and Toxicology,Academy of Military Medical Sciences,Beijing 100850,China;Regiment 95865 of PLA,Beijing 102200,China;Regiment 32292 of PLA,Mudanjiang 157000,China;Regiment 32265 of PLA,Guangzhou 510000,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,高毒物质对抗药物研究国家重点实验室,北京100850 [2]中国人民解放军95865部队,北京102200 [3]中国人民解放军32292部队,黑龙江牡丹江157000 [4]中国人民解放军32265部队,广东广州510000

出　　处：《中国药理学与毒理学杂志》2021年第2期109-115,共7页Chinese Journal of Pharmacology and Toxicology

基　　金：北京市科技新星项目(Z191100001119105)。

摘　　要：目的评价不同剂量VX对小鼠脑和外周血乙酰胆碱酯酶(AChE)的活性和含量随时间变化的影响。方法小鼠sc给予VX 5,10和16μg·kg^(-1),分别于10 min,1 h,4 h,24 h,48 h和72 h记录体重和脑重,计算脑系数;Ellman法测定AChE活性;ELISA测定AChE含量;并计算被VX抑制的AChE含量和VX消耗量。结果在染毒后72 h内,各组小鼠体重、脑重和脑系数均未见明显变化。与同剂量下染毒10 min相比,VX 5,10和16μg·kg^(-1)组外周血AChE活性抑制率在各时间点均明显下降(P<0.05,P<0.01)。与同剂量染毒10 min比较,VX 16μg·kg^(-1)组脑AChE活性抑制率在4~72 h显著下降(P<0.01);10μg·kg^(-1)组在48和72 h显著下降(P<0.01);5μg·kg^(-1)组在24 h显著上升(P<0.01),而在其他时间点无明显变化。各剂量组脑和外周血中VX的消耗量均在48 h达到最低,在72 h略有回升。VX 16μg·kg^(-1)组VX消耗量仅占染毒剂量的28%。结论在染毒后48 h内大部分毒剂残留在体内,72 h后可能再次引起中枢AChE抑制。因此,对于神经性毒剂VX中毒的救治,建议急性中毒症状控制后,在染毒48 h内再次给予抗毒药物。OBJECTIVE To evaluate the activity and content of brain and peripheral blood acetylcholinesterase(AChE)with time in mice exposed to different doses of VX.METHODS Mice were sc given VX 5,10 and 16μg·kg^(-1).The body mass and brain mass were recorded at 10 min,1 h,4 h,24 h,48 h and 72 h to calculate the brain coefficient.The activity of AChE was detected using the Ellman method.The content of AChE was detected by ELISA.The amount of AChE inhibited by VX and the consumption of VX were calculated.RESULTS Brain mass and brain coefficient did not change significantly in any group within 72 h of VX exposure.Compared with 10 min in the same dose group,the inhibition rate of AChE in peripheral blood in VX 5,10 and 16μg·kg^(-1) groups decreased significantly at each time point(P<0.05,P<0.01).Compared with 10 min in the samedose group,the inhibition rate of brain AChE decreased significantly within 4-72 h in the 16μg·kg^(-1) group(P<0.01),at 48 and 72 h in the 10μg·kg^(-1) group(P<0.01),but increased significantly at 24 h in the 5μg·kg^(-1) group(P<0.01).There was no significant change at other time points.The consumption of VX in the brain and peripheral blood of each group reached the lowest at 48 h,and slightly increased at 72 h.In the VX 16μg·kg^(-1) group,the consumption of VX was only 28%of the total dose.CONCLUSION After exposure,the inhibition rate of AChE in the brain and peripheral blood of each dose group and the actual consumption of VX reach the lowest point at 48 h and then increase at 72 h,indicating that most of the agents do not participate in the reaction within 48 h.The residual agents after 72 h may cause the inhibition of AChE in the central nervous system again.Therefore,for the treatment of VX poisoning,it is suggested that after the symptoms of acute poisoning are controlled,the corresponding dose of anti-nerve agent drugs should be given again within 48 h to antidote VX residues that do not bind to AChE temporarily.

关 键 词：神经性毒剂 VX 抑制剂 乙酰胆碱酯酶 重活化 

分 类 号：R827.12[医药卫生—临床医学]