沙林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 sarin

作　　者：李尧 黄静宜[1] 邢欢纯 章子男 王琦 王永安[1] 杨军 LI Yao;HUANG Jing-yi;XING Huan-chun;ZHANG Zi-nan;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 32292 of PLA,Heilongjiang Province,Mudanjiang 157000,China;Regiment 95865 of PLA,Beijing 102200,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32292部队,黑龙江牡丹江157000 [3]中国人民解放军95865部队,北京102200 [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》2020年第9期687-693,共7页Chinese Journal of Pharmacology and Toxicology

基　　金：北京市科技新星项目(Z191100001119105)。

摘　　要：目的通过精确测量不同剂量沙林染毒后小鼠不同时间内脑及外周血乙酰胆碱酯酶(AChE)活性和含量,研究其剂量、抑制效应及AChE含量和活性随时间变化的规律。方法小鼠sc给予沙林100,200,250和320μg·kg^-1,分别于10 min,1 h,4 h,24 h,48 h和72 h记录体质量和脑重,计算脑系数;Ellman法测定脑组织和外周血中AChE活性;ELISA法测定脑组织和外周血中AChE含量。结果沙林320μg·kg^-1组小鼠在10 min内全部死亡,其余各组小鼠未见明显体质量差异和脑萎缩。各组血AChE抑制率随染毒时间的延长而显著下降,与10 min时相比,100μg·kg^-1组在1 h即出现显著降低(P<0.01),200和250μg·kg^-1组在4 h开始出现显著降低(P<0.01)。与各组10 min时脑AChE活性相比,1 h后100μg·kg^-1组脑AChE抑制率显著上升(P<0.01);4 h后200μg·kg^-1组脑AChE抑制率显著上升(P<0.05);与4 h相比,24 h后各染毒组抑制率均明显下降(P<0.05),48 h后各组抑制率均急剧上升(P<0.05)。在各染毒剂量下,AChE含量在染毒4 h后均恢复正常水平。染毒72 h内,100和200μg·kg^-1组血和脑内消耗的沙林均在1 h后出现下降(P<0.01);而250μg·kg^-1组血和脑内消耗的沙林均在24 h后出现下降(P<0.01)。100和200μg·kg^-1组脑内与沙林结合的AChE数量均在1 h后出现下降(P<0.01);250μg·kg^-1组在24 h后出现下降(P<0.01)。结论随沙林染毒剂量的增加,脑内沙林对AChE抑制增加,但最高仅占染毒剂量的2%,大部分沙林还存留在体内持续抑制AChE,在染毒4和48 h 2次达到高峰。因此对于神经毒剂中毒救治,建议控制急性中毒症状后,在相应时间内多次给予抗毒药物。OBJECTIVE To study how the dose,inhibitory effect and activity of sarin change with time and explore the activity and content of central and peripheral acetylcholinesterase(AChE)in mice exposed to different doses of sarin that were measured accurately.METHODS(1)The body mass and brain weight of mice were recorded after subcutaneous injection of sarin of different concentrations(100,200,250 and 320μg·kg^-1)at different time points(10 min,1 h,4 h,24 h,48 h and 72 h),and the organ coefficient was calculated.(2)The activity of ACh E was detected by Ellman method.(3)The content of AChE was detected by ELISA.RESULTS(1)After exposure to sarin,all the mice in the 320μg·kg^-1 group died in 10 min,but there was no significant difference in body mass or brain atrophy between the other groups.(2)Compared with exposure of 10 min,the inhibition rate of blood enzyme decreased significantly with the exposure time,and the difference was statistically significant in the 100μg·kg^-1 group at 1 h(P<0.01),and in the 200 and 250μg·kg^-1 groups at 4 h(P<0.01).(3)Compared with exposure of 10 min,the inhibitory rate of brain enzyme in the 100μg·kg^-1 group decreased significantly after 4 h(P<0.05),but decreased significantly after 24 h and increased sharply in each exposed group after 48 h(P<0.05).(4)At different doses,AChE content returned to normal after 4 h.The amount of sarin consumed in the blood and brain of the 100 and 200μg·kg^-1 groups decreased after 1 h,while that of the 250μg·kg^-1 group decreased after 24 h.The amount of AChE bound to sarin in the 100 and 200μg·kg^-1 groups decreased after 1 h,but after 24 h in the 250μg·kg^-1 group(P<0.01).CONCLUSION With the increase of sarin dose,the inhibition of AChE on the brain is increased,but the highest dose only accounts for 2%of the whole dose.Most of the sarin remained in the body to continue to inhibit AChE and reaches two peaks at 4 and 48 h.Therefore,for the treatment of sarin poisoning,it is recommended that anti-sarin drugs be given several times in the co

关 键 词：沙林 胆碱酯酶 抑制剂 老化 酶活性 

分 类 号：R827.12[医药卫生—临床医学]