目的通过观察不同价态无机砷染毒大鼠肝脏砷形态代谢产物分布,初步探讨不同价态无机砷体内代谢和毒性机制。方法 W istar大鼠42只,随机分成7组,于染砷3个月后,处死动物,迅速摘取肝脏,于-80℃冷藏;采用高效液相色谱-氢化物发生原子荧光光谱法(HPLC-HGAFS)测定并比较各组染砷大鼠肝脏中砷形态代谢产物的水平和分布,计算一甲砷酸(MMA)加标回收率评价结果准确度;通过肝脏中总砷含量评价砷蓄积能力;分析肝脏中甲基化代谢指标一甲基化率(PM I)和二甲基化率(SM I)水平,评价各组间甲基化代谢能力或途径差异。结果亚砷酸钠与砷酸钠高、中、低剂量组总砷水平分别为(1 142.9±50.4)、(484.6±37.4)、(323.3±20.2)和(3 695.2±345.9)、(1833.8±229.6)、(1 170.5±77.4)ng/g,砷酸钠各剂量组总砷水平明显高于亚砷酸钠组(P<0.05);亚砷酸钠中、低剂量组iAs3+[(118.4±23.9)、(252.3±14.3)]ng/g和二甲砷酸(DMA)[(353.2±45.6)、(55.2±10.6)]ng/g含量均低于砷酸钠组(P<0.05);亚砷酸钠中、低剂量组MMA含量高于砷酸钠组(P<0.05),同时,亚砷酸钠各剂量组PMI和SMI均低于砷酸钠各剂量组(P<0.05)。结论五价砷代谢产物在肝脏蓄积能力强于三价砷,五价砷在肝脏一甲基化及二甲基化代谢能力强于三价砷,具有较大肝脏毒性。 OBJECTIVE: To observe the distribution of arsenic metabolites in liver of rats with different valences of inorganic arsenic exposure and to explore the mechanism of metabolism and toxicity of different valence inorganic arsenic. Methods Forty-two Wistar rats were randomly divided into 7 groups. Animals were sacrificed after 3 months of arsenic exposure, and the liver was quickly harvested at -80 ℃. High-performance liquid chromatography-hydride generation atomic emission spectrometry (HPLC -HGAFS) were used to determine and compare the levels and distribution of arsenic metabolites in the liver of arsenic-exposed rats in each group, and the accuracy of the evaluation of the recovery of arsenic monoxide (MMA) was calculated. The arsenic accumulation capacity was evaluated by the total arsenic in the liver The methylation rate (PM I) and the rate of dimethylation (SM I) of methylation metabolism in the liver were analyzed to evaluate the differences of methylation metabolic capacity or pathways in each group. Results The total arsenic levels of sodium arsenite and sodium arsenate groups were (1 142.9 ± 50.4), (484.6 ± 37.4), (323.3 ± 20.2) and (3695.2 ± 345.9), (1833.8 ± 229.4), and (1705 ± 77.4) ng / g respectively. The total arsenic levels in all the sodium arsenate groups were significantly higher than those in the sodium arsenite group (P <0.05) 23.9, 252.3 ± 14.3 ng / g and DMA, 353.2 ± 45.6 and 55.2 ± 10.6 ng / g, respectively, were lower than those of sodium arsenate group (P <0.05). The contents of MMA in middle and low doses of sodium arsenite were higher than those of sodium arsenate (P <0.05). Meanwhile, the PMI and SMI in each dosage of sodium arsenite were lower than those of sodium arsenite (P <0.05). Conclusions The pentavalent arsenic metabolites are more capable of accumulating in the liver than trivalent arsenic. Pentavalent arsenic is more capable of monomethylating and dimethylating in the liver than trivalent arsenic, and has a higher hepatic toxicity.