几种氨基甲酰化乙酰胆碱酯酶(AChE)的体内代谢过程

METABOLISM OF SOME CARBAMYLATED ACETYLCHOLINESTERASES(AChEs) IN VIVO

目的：观察吡啶斯的明、毒扁豆碱、卡巴呋喃和灭多威四种氨基甲酸酯类化合物其氨基甲酰化乙酰胆碱酯酶（AChE）的体内代谢过程，为氨基甲酸酯类杀虫剂中毒诊断和用药提供理论依据。[f11]方法：[f0]以小鼠为实验对象，其红细胞AChE为酶源，上述四种氨基甲酸酯类化合物为酶抑制剂，改进微量DTNB法测定中毒酶活性，观察不同时间小鼠体内AChE酶抑制率，并对时间进行曲线拟合，同时计算半衰期。[f11]结果：[f0]酶抑制作用于30-45min达到最大，中毒酶体内代谢过程以二甲基氨基甲酰化AChE，即吡啶斯的明中毒酶最慢，半衰期为142.7min；而单甲基氨基甲酰化AChE代谢则相对较快，毒扁豆碱、卡巴呋喃和灭多威中毒酶半衰期分别为102.7min、82.5min、和31.1min，数小时（1.7～7.6小时）后，中毒酶活性可恢复90%以上。[f11]结论：[f0]氨基甲酸酰化AChE的体内代谢过程除与氨基甲酸酯类化合物的结构有关外，还可能有其他的决定因素，且代谢过程较磷酰化AChE快；同时，灭多威作用机理的特殊性也值得临床重视。

Objective: In order to diagnose and treat better in carbamates intoxication, metabolism was investigated of pyridostigmine,physostigmine,carbofunan and methomyl-inhibited acetylcholinesterases(AChEs) in vivo. Methods: Using mice erythrocyte as objects, pyridostigmine, physostigmine, carbofunan and methomyl as inhibitors, improving micro-DTNB method to measure AChE inhibition, and work out half-life of carbamylated AChEs. Results: Inhibition reached maximum at 30-45min. Metabolism of bimethyl-carbamylated AChE, pyridostigmine-inhibited AChE, was slower, whose half-life was 142.7min; metabolism of monomethyl-carbamylated AChEs was faster relatively, and half-life of physostigmine, carbofunan and methmyl-inhibited AChEs were 102.7min,82.5min and 31.1min, respectively. After several hours (1.7～ 7.6 hours), activity of inhibited AChEs could restore 90% above. Conclusion: Metabolism of carbamylated AChEs was related to other factors besides carbamates structure, and far faster than that of phosphated AChE, which should be emphasized in clinical working. In addition, peculiarity of methomyl action mechanism also should be stressed.