尼莫地平对兔血中梭曼的消除及[^3H]梭曼在小鼠组织分布的影响

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.

Influence of nimodipine on elimination of soman in rabbit blood and distribution of [3H]soman in mice

AIM: To investigate the effect of nimodipine on the elimination of soman in rabbit blood and distribution of [3H]soman in mice. METHODS: Chirasil capillary gas chromatographic analysis method with large volume injections was used to determine the concentration of C(+/-)P(-)soman in rabbit blood. [3H]soman trace method was used to study the effect of nimodipine on soman distribution in mice. RESULTS: Nimodipine (10 mg/kg, ip, 1 h pre-treated) could significantly reduce the concentration of C(+/-)P(-)soman in rabbit blood from (54+/-13) to (19+/-12) microg/L blood at 15 s after soman injection (43.2 microg/kg, iv). Nimodipine could increase clearance rate [CL(S)] from (20.8+/-1.5) to (31+/-11) mL/kg/s and reduce AUC of C(+/-)P(-)soman from (2.08+/-0.15) to (1.6+/-0.4) mg/s. Nimodipine (10 mg/kg, ip, 1 h pre-treated) treatment could significantly reduce the distribution amount of bound [3H]soman in plasma, brain, lung, and liver, moreover increased the distribution amount of bound [3H]soman in small intestine during 0-120 min after mice received [3H]soman (0.544 GBq*119 microg/kg, sc) compared to soman control group. CONCLUSION: Nimodipine might alter the distribution of soman and reduce the initial concentration of soman in rabbit blood, then accelerated the metabolic detoxication of soman.