论文部分内容阅读
目的 :考察 80 18对梭曼兔的毒代动力学及小鼠组织分布的影响 ,探索 80 18对梭曼代谢解毒作用机制。方法 :大进样量气相色谱仪及手性毛细管柱氮磷检测器测定兔静脉染毒后血中及小鼠皮下染毒后脑与膈肌中游离C(± )P(_)梭曼 ;同位素示踪法测定结合 [3H]梭曼在小鼠组织中的分布。结果 :与梭曼对照组相比 ,80 18(1mg kg ,im 10min预给药 )在中毒后 15s时能使梭曼浓度由 (5 3.6± 13.3)mg ml显著下降到 (2 6 .2± 9.6 7)mg ml。毒代动力学参数表明 :80 18使C(± )P(_)梭曼的CL由 (2 0 .8± 1.5 )ml (kg·s)显著增加到 (38.2± 15 .3)ml (kg·s) ;使AUC由 (2 .0 8± 0 .15 )mg·s L显著下降到 (1.30± 0 .5 6 4 )mg·s L。 80 18预给药在小鼠皮下梭曼染毒后 30 ,90及 12 0s时 ,能使膈肌中游离C(± )P(_)梭曼的浓度由 74 .7,70 .5 ,88.7ng g降低到 5 4 .5 ,4 5 .6 ,5 0 .0ng g,但在以上时间点对脑中游离C(± )P(_)梭曼的浓度却没有显著的影响。同位素示踪试验表明 ,80 18能显著升高小鼠 [3H]梭曼皮下染毒 (0 .5 4 4GBq ,119μg kg) 0～12 0min后血浆与小肠中结合 [3H]梭曼的分布。结论 :80 18可能通过改变梭曼的分布 ,降低了血中梭曼的初始浓度而起到促进梭曼代谢解毒的作用。
OBJECTIVE: To investigate the effect of 80 18 on the toxicokinetics and tissue distribution of soman, and to explore the mechanism of 80 18 on soman detoxification. Methods: The free C (±) P (_) soman in the blood and mouse subcutaneously after intravenous injection of rabbit vein was determined by large sample volume gas chromatograph and chiral capillary column nitrogen and phosphorus detector. Determination of the binding of [3H] soman in mouse tissues. RESULTS: Compared with the soman control group, the soman concentration significantly decreased from (5 3.6 ± 13.3) mg ml to (26.2 ± 1) mg / ml at 15 s after poisoning 9.6 7) mg ml. Toxicokinetic parameters indicated that 80 18 significantly increased CL of C ± P () soman from (20.8 ± 1.5) ml (kg · s) to (38.2 ± 15.3) ml (kg · S). The AUC was significantly decreased from (2.08 ± 0.155) mg · s L to (1.30 ± 0.546) mg · s-1. 80 18 The pretreatment could make the free C (±) P (_) soman concentration in the diaphragm increased from 74.7, 70.5, 88.7 ng at 30, 90 and 120 s after subcutaneous soman administration g to 54.5, 45.5, 60.0 ng g, but there was no significant effect on the free C (±) P (_) soman concentration in the brain at the above time points. Isotope tracing experiments showed that 80 18 significantly increased [3H] -soman binding in plasma and small intestine after [3H] soman subcutaneous exposure (0.54 4GBq, 119 μg kg) at 0-12Omin. Conclusion: 80 18 may play an important role in promoting Soman metabolism and detoxification by changing the distribution of soman and decreasing the initial concentration of soman in blood.