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目的:研究甲基莲心碱(Nef)对敌敌畏(DDVP)抑制兔胆碱酯酶(ChE)毒效动力学的影响,探讨Nef重活化被抑制的ChE在体和离体实验的相关性。方法:采用比色法测定兔血中 DDVP浓度,计算毒代动力学参数。用Ellman氏法测定血中ChE活力单位,绘制在体的毒效动力学曲线和离体的量效曲线,观察Nef对各曲线的影响。结果:Nef对DDVP毒代动力学没有影响,而ig 12.5 mg/kg DDVP中毒家兔应用Nef(7.5 mg/kg)和氯磷定(2-PAM·Cl 50 mg/kg)解救后被抑制的ChE毒效动力学曲线斜率增大3倍,与未施救组比较差异非常显著(P<0.01)。离体实验中Nef使DDVP抑制的ChE累积量效曲线右移,最大抑制反应显著降低。离体的浓度-效应关系与在体的毒效关系结果趋势相似,两直线回归所得b值不具差异(P>0.05)。结论:Nef重活化被抑制的ChE使其毒效动力学曲线下移,可采用离体实验方法初步研究ChE复能剂的重活化效应。
Objective: To investigate the effect of Nef on DDEC inhibition of the cholinesterase (ChE) toxicokinetics and to explore the correlation between Nef reactivation-inhibited ChE in vitro and in vivo. Methods: DDVP concentration in rabbit blood was determined by colorimetric method, and the toxicokinetic parameters were calculated. Ellman’s method was used to measure the activity units of ChE in the blood, and the pharmacodynamic kinetics curve and in vitro volume-effect curve were plotted to observe the effect of Nef on each curve. RESULTS: Nef had no effect on the DDVP toxicokinetics, whereas ig 12.5 mg / kg DDVP poisoned rabbits were inhibited after being rescued with Nef (7.5 mg / kg) and chlorpromazine (2-PAM · Cl 50 mg / kg) ChE toxicokinetic curve slope increased 3 times, compared with the non-rescue group, the difference was significant (P <0.01). In vitro experiments Nef DDEC inhibit ChE cumulative dose-response curve to the right, the maximum inhibitory response was significantly reduced. The in vitro concentration-effect relationship was similar to that in vivo, and there was no difference in b value between the two linear regression (P> 0.05). CONCLUSION: Nef reactivation is inhibited by the ChE to make its kinetic curve down kinetics, in vitro experiments can be used to study the initial reactivation of ChE agent.