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目的:考察尼莫地平对兔血中梭曼的消除及结合[~3H]梭曼在小鼠组织分布的影响,以探索尼莫地平对梭曼代谢解毒的作用.方法:以二异丙基氟磷酸酯(DFP)为内标,用大进样量手性毛细管柱气相色谱法测定兔梭曼静脉染毒后血中游离C(±)P(-)梭曼浓度.同位素示踪法测定结合[~3H]梭曼在小鼠组织中的分布.结果:尼莫地平(10 mg/kg,ip,预给药1小时)使兔梭曼染毒(43.2 μg/kg,iv)15 s后,血中游离C(±)P(-)梭曼浓度从(54±13)μg/L下降到(19±12)μg/L,使血中C(±)P(-)梭曼的清除率从(20.8±1.5)mL·kg~(-1)·s~(-1)增加到(31±11)mL·kg~(-1)·s~(-1),从而使AUC从(2.08±0.15)mg·s·L~(-1)降低到(1.6±0.4)mg·s·L~(-1).尼莫地平(10 mg/kg,ip,预给药1小时)能显著降低在[~3H]梭曼皮下染毒(0.544 GBq·119 μg/kg)0-120 min后小鼠血浆、脑、肺及肝脏中结合[~3H]梭曼的分布,而小肠中结合[~3H]梭曼的分布却显著升高.结论:尼莫地平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 nimodipine on the elimination of soman in rabbit blood and the effect of binding of [~ 3H] soman on the tissue distribution of mouse so as to explore the effect of nimodipine on soman metabolism and detoxification.METHODS: Determination of free C (±) P (-) soman concentration in rabbit venous blood using a large sample of chiral capillary gas chromatography with fluorophosphate (DFP) as the internal standard. The binding of [~ 3H] soman in mouse tissues was observed.Results: Nimodipine (10 mg / kg, ip, pre-administration for 1 hour) The soman concentration in the blood decreased from (54 ± 13) μg / L to (19 ± 12) μg / L in the blood, and the blood C (±) P The clearance rate increased from (20.8 ± 1.5) mL · kg -1 · s -1 to (31 ± 11) mL · kg -1 · s -1, (2.08 ± 0.15) mg · s · L -1 to (1.6 ± 0.4) mg · s · L -1 Nimodipine (10 mg / kg, ip for 1 hour) Can significantly reduce the distribution of [~ 3H] soman in mice plasma, brain, lung and liver 0-120 min after [~ 3H] soman subcutaneous exposure (0.544 GBq · 119 μg / kg) The binding of [~ 3H] soman was significantly increased.Conclusion: Nimodipine may be changed by changing Man distribution, reducing the initial concentration in the blood of soman and play the role of promoting the metabolism, detoxification soman.