沙林对猴全血乙酰胆碱酯酶抑制的老化及重活化

Aging and reactivation of sarin-inhibited acetylcholinesterase in monkey blood

目的研究沙林对猴全血乙酰胆碱酯酶(AChE)的抑制,磷酰化酶的老化速率及肟类药物的重活化作用。方法 5,5-连硫代-双-2-硝基苯甲酸(DTNB)法测定AChE活性。结果沙林抑制猴全血AChE的IC50值为6.3×10-8mol/L,IC90值为1.5×10-7mol/L。在0.1、0.33和1 mmol/L的浓度下,氯解磷定对沙林抑制猴全血AChE的重化活率分别为16%、45%和83%;双复磷对沙林抑制猴全血AChE的重化活率分别为18%、39%和70%;碘解磷定对沙林抑制猴全血AChE的重化活率分别为14%、41%和72%。采用1 mmol/L的氯解磷定为重活化剂时,沙林抑制猴全血AChE磷酰化酶的半老化时间约为12 h。结论沙林中毒后应尽早使用氯解磷定等肟类重活化剂。在低浓度0.1 mmol/L时,双复磷重活化效果最好;随着不同重活化剂浓度的增加,氯解磷定显示出较好的重活化效果。氯解磷定为重活化剂时,急性中毒症状控制后,建议应在12 h内重复使用。

Objective To study the inhibition of acetylcholinesterase（AChE） by sarin,aging rates of phosphorus acylase and reactivation of phosphorus acylase by oxime drugs in monkey blood.Methods The activity of AChE was detected by DTNB method.Results The IC50 and IC90 value of inhibition of AChE by sarin in monkey blood was 6.3×10-8 mol/L and 1.5×10-7 mol/L,respectively.At the concentration of 0.1 mmol/L,0.33 mmol/L and 1 mmol/L,the reactivation rate of pralidoxime（pyraloxime）chloride on sarin-inhibited AChE in monkey blood was 16%,45% and 83%,respectively,the reactivation rate of obidoxime chloride on inhibited AChE was 18%,39% and 70%,and the respectively,and the reactivation rate of pralidoxime（pyraloxime） iodide on inhibition of AChE was 14%,41% and 72%,respectively.The half aging time of phosphorus acylase of sarin-inhibited AChE in monkey blood was about 12 hours using 1 mmol/L pralidoxime chloride as the reactivator.Conclusion Such oximes as pralidoxime chloride should be used soon after sarin poisoning.The reactivation effect of obidoxime chloride is better than that of pralidoxime chloride and pralidoxime iodide at low concentrations,but pralidoxime chloride shows the best effectiveness with the increasing concentration.Acute poisoning symptoms can be controlled by pralidoxime chloride,which should be repeated within 12 hours.