亚慢性饮水砷暴露小鼠组织形态砷的蓄积与分布

Accumulation and distributions of arsenic species in tissue of mice subchronically exposed to arsenicin drinking water

目的探讨亚慢性饮水砷暴露小鼠各组织中无机砷及其代谢产物的蓄积与分布规律。方法将40只健康8周龄清洁级昆明雌性小鼠按体重随机分为对照(生理盐水)组和50、100、200 mg/L亚砷酸钠染毒组,每组10只。采用亚砷酸钠自由饮水方式染毒,连续染毒3个月。检测小鼠肝脏、肾脏、脾脏、肺脏、膀胱、大脑皮层、小脑和海马组织中五价无机砷(pentavalent inorganic arsenic,iAs5+)、三价无机砷(trivalent inorganic arsenic,iAs3+)、单甲基胂酸(monomethylated arsenic,MMA)和二甲基胂酸(dimethylated arsenic,DMA)的含量,并计算总砷(total arsenic,TAs)含量。结果各浓度亚砷酸钠暴露组小鼠肝脏中TAs、iAs3+和DMA的含量与对照组比较,差异均无统计学意义(P>0.05)。与50 mg/L亚砷酸钠暴露组比较,100、200 mg/L亚砷酸钠暴露小鼠肾脏、肺脏和膀胱中TAs和DMA含量均升高,差异有统计学意义(P<0.05);与100 mg/L亚砷酸钠暴露组比较,200 mg/L亚砷酸钠暴露小鼠肾脏TAs和DMA含量均升高,差异有统计学意义(P<0.05)。与50 mg/L亚砷酸钠暴露组比较,200 mg/L亚砷酸钠暴露小鼠脾脏TAs和DMA含量以及膀胱iAs3+含量均升高,差异有统计学意义(P<0.05)。与100 mg/L亚砷酸钠暴露组比较,200 mg/L亚砷酸钠暴露小鼠膀胱TAs、iAs3+和DMA含量均升高,差异有统计学意义(P<0.05)。与50 mg/L亚砷酸钠暴露组比较,100 mg/L亚砷酸钠暴露小鼠大脑皮层和小脑中TAs含量及200 mg/L亚砷酸钠暴露小鼠大脑皮层和小脑中TAs和DMA的含量均升高,差异有统计学意义(P<0.05);与100 mg/L亚砷酸钠暴露组比较,200 mg/L亚砷酸钠暴露小鼠小脑TAs和DMA含量均升高,差异有统计学意义(P<0.05)。与50 mg/L亚砷酸钠暴露组比较,200 mg/L亚砷酸钠暴露小鼠海马TAs、MMA和DMA含量均升高,差异有统计学意义(P<0.05);与100 mg/L亚砷酸钠暴露组比较,200 mg/L亚砷酸钠暴露小鼠海马MMA含量升高,差异有统计学意义(P<0.05)。各浓度亚砷酸钠暴露组小鼠组织中iAs3+以及肺脏和膀胱中MMA的含量间比较,差异均无统计学意义(P>0.05)。随着亚砷酸钠暴露浓度的升高,小鼠各组织中TAs和DMA含量均呈上升趋势,膀胱和海马中MMA亦呈上升趋势。100、200 mg/L亚砷酸钠暴露组小鼠各组织中TAs和DMA的含量由高到低依次为膀胱>肝脏>肺脏>肾脏>脾脏;部分脑区组织中TAs和DMA的含量由高到低依次为大脑皮层>海马>小脑。200 mg/L亚砷酸钠暴露组小鼠肺脏、100和200 mg/L亚砷酸钠暴露组小鼠膀胱以及50、100和200 mg/L亚砷酸钠暴露组小鼠海马中可检测出MMA,其它各浓度亚砷酸钠暴露组小鼠组织中MMA均未检出所有亚砷酸钠暴露组小鼠组织中均未检出iAs5+。结论亚慢性饮水砷暴露小鼠组织中形态砷的蓄积与分布具有明显的组织特异性,并且无机砷及其代谢产物能够穿越血脑屏障,区域特异性地蓄积在大脑皮层、小脑和海马组织。

Objective To investigate the accumulation and distribution pattern of inorganic arsenic and its metabolites in tissues of mice subchronically exposed to arsenic in drinking water.Methods A total of 40 healthy female Kunming mice aged eight weeks were randomly assigned to four groups by body weight,which were control group(normal saline),50,100 and 200 mg/L sodium arsenite(NaAsO2)group,ten in each group.Mice drank water containing NaAsO2 freely for three months,then pentavalent inorganic arsenic(iAs5+),trivalent inorganic arsenic(iAs3+),monomethylated arsenic(MMA),dimethylated arsenic(DMA)in liver,lung,spleen,kidney,urinary bladder,cerebral cortex,cerebellum and hippocampus were detected,as well as total arsenic(TAs)levels were calculated.Results Compared with control group,the levels of TAs,iAs3+and MMA were not significantly different in liver of mice exposed to NaAsO2 with various concentrations(P>0.05).TAs and DMA levels in kidney,lung and urinary bladder of 100 and 200 mg/L NaAsO2-exposed mice were significantly higher than 50 mg/L NaAsO2 group(P<0.05).TAs and DMA levels in kidney of 200 mg/L NaAsO2-exposed mice were significantly higher than 100 mg/L NaAsO2 group(P<0.05).TAs and DMA levels in spleen,as well as iAs3+levels in urinary bladder of 200 mg/L NaAsO2-exposed mice were significantly higher than 50 mg/L NaAsO2 group(P<0.05).TAs,iAs3+and DMA levels in urinary bladder of 200 mg/L NaAsO2-exposed mice were significantly higher than 100 mg/L NaAsO2 group(P<0.05).TAs levels in cerebral cortex and cerebellum of 200 mg/L NaAsO2-exposed mice,as well as TAs and DMA levels in cerebral cortex and cerebellum of 200 mg/L NaAsO2-exposed mice were significantly higher than 50 mg/L NaAsO2 group(P<0.05);TAs and DMA levels in cerebellum of 200 mg/L NaAsO2-exposed mice were significantly higher than 100 mg/L NaAsO2 group(P<0.05).TAs,iAs3+and DMA levels in hippocampus of 200 mg/L NaAsO2-exposed mice were significantly higher than 50 mg/L NaAsO2 group(P<0.05).MMA levels in hippoampus of 200 mg/L NaAsO2-exposed mice were significantly higher than 100 mg/L NaAsO2 group(P<0.05).There were not significant differences among iAs3+levels in all tissues,as well as MMA levels in lung and bladder of mice exposed to NaAsO2 with various concentrations(P>0.05).The contents of TAs and DMA in various tissues,as well as MMA in urinary bladder and hippocampus increased with the increases of NaAsO2 exposure doses.Average levels of TAs and DMA in tissues of 100 and 200 mg/L NaAsO2-exposed mice ranked as urinary bladder﹥liver﹥lung﹥kidney﹥spleen,and also ranked as cerebral cortex﹥hippocampus﹥cerebellum in brain regions.MMA was not detected in tissues of mice exposed to NaAsO2 with all concentrations,except in lung of 200 mg/L NaAsO2 group,urinary bladder of 100 and 200 mg/L NaAsO2 group,as well as hippocampus of 50,100 and 200 mg/L NaAsO2 group.iAs5+was not detected in tissues of mice exposed to NaAsO2 with all concentrations.Conclusion The accumulation and distribution of arsenic species in tissues of mice subchronically exposed to arsenic in drinking water is tissue-specific,and inorganic arsenic and its metabolites can pass through the blood brain barrier and region-specifically accumulated in cerebral cortex,cerebellum and hippocampus.