目的探讨急性砷暴露小鼠尿砷排泄及其甲基化代谢模式。方法健康雌性昆明种小鼠一次性灌胃染毒亚砷酸钠(NaAsO2),染毒剂量为2.5、5.0、10.0、20.0 mg/kg,染毒时间为12、24、48、72 h。染毒结束前一天将小鼠放入代谢笼并收集24 h尿样(12 h组收集12 h尿样)。采用超低温捕集-氢化物发生-原子吸收分光光度法分别测定尿中的无机砷(inorganic arsenic,iAs)、一甲基砷(monomethylated arsenic,MMA)和二甲基砷(dimethylated arsenic,DMA)含量,并计算iAs%、MMA%、DMA%、一甲基化率(primary methylation index,PMI)和二甲基化率(secondary methylation index,SMI)。结果急性砷暴露小鼠,随着染砷剂量增加,尿总砷(T-As)含量、iAs%、MMA%明显增加,DMA%和SMI逐渐降低,PMI基本保持不变;而一次性砷染毒后,随时间的延长,尿T-As含量、iAs%、MMA%逐渐降低,DMA%、PMI和SMI明显增加。24 h内尿砷大部分排泄,其百分含量及甲基化率都基本在同一水平,48 h和72 h的尿砷排泄量很少,其百分含量及甲基化率都基本一致。结论急性砷暴露小鼠尿砷排泄具有明显的剂量-效应和时间-效应关系;高砷暴露可以抑制砷的甲基化代谢;24 h内尿砷含量可作为判断急性砷中毒体内砷负荷的指标。
Objective To investigate the level of urine arsenic excretion and methylated metabolism pattern in mice exposed to acute arsenic.Methods Healthy female Kunming mice were exposed to sodium arsenite(NaAsO2) by intragastric infusion at doses of 2.5 mg/kg,5.0 mg/kg,10.0 mg/kg and 20.0 mg/kg,the exposure time for each group were 12 hours,24 hours,48 hours and 72 hours.The mice were placed in metabolic cages and urine samples of 24-hour group were collected(urine samples of 12 hours were collect from 12-hour group) before the end of exposure day.The level of inorganic arsenic(iAs),monomethylated arsenic(MMA) and dimethylated arsenic(DMA) in urine were determined by cold trap hydride generation atomic absorption spectrophotometer respectively,the level of T-As,iAs%,MMA%,DMA%,primary methylation index(PMI) and secondary methylation index(SMI) were calculated.Results Urine T-As level,iAs% and MMA in the mice exposed to acute arsenic increased significantly with the increase of arsenic concentration,but DMA% and SMI decreased with stable PMI.With the increase of time after exposure,urine T-As level,iAs% and MMA% gradually decreased,while DMA%,PMI and SMI increased significantly.The most urine arsenic were excreted within 24 hours,and its percentage content and methylation index were at same level,the level of urine arsenic excretion was very low in 48-hour and 72-hour groups and their percentage content and methylation index were at same level.Conclusion Urine arsenic excretion in mice exposed to acute arsenic has obvious dose-effect relation and time-effect relation;High concentration of arsenic exposure may effectively inhibit methylated metabolism,and urine arsenic content within 24 hours could be used as an indicator to determine the arsenic burden of an acute arsenic poisoned body.