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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 urinary arsenic excretion and methylation patterns in acute arsenic-exposed mice. Methods Healthy female Kunming mice were intragastrically infused with sodium arsenite (NaAsO2) at doses of 2.5, 5.0, 10.0 and 20.0 mg / kg for 12, 24, 48 and 72 h. The day before the end of the exposure, mice were placed in metabolic cages and 24 h urine samples were collected (12 h urine samples collected in 12 h). The concentrations of inorganic arsenic (iAs), monomethylated arsenic (MMA) and dimethylated arsenic (DMA) in urine were determined by ultra-low temperature capture-hydride generation- atomic absorption spectrophotometry , And calculate iAs%, MMA%, DMA%, primary methylation index (PMI) and secondary methylation index (SMI). Results With the increase of arsenic dose, the contents of total arsenic (T-As), iAs% and MMA in acute arsenic-exposed mice increased significantly, while DMA% and SMI decreased gradually while PMI remained unchanged. Toxicity, urine T-As content, iAs%, MMA% gradually decreased and DMA%, PMI and SMI increased obviously with the prolongation of time. Most excretion of urinary arsenic within 24 h, the percentage and methylation rate were basically the same level, 48 h and 72 h urinary excretion of very little, its percentage and methylation rate are basically the same. Conclusion Arsenic excretion in acute arsenic exposure mice has obvious dose-effect and time-effect relationship; high arsenic exposure can inhibit arsenic methylation metabolism; 24 h urine arsenic content can be used as an indicator of arsenic load in acute arsenic poisoning .