急性经口无机砷暴露小鼠肝肾肺等组织中形态砷的动态变化

Dynamic changes of arsenic species in tissues of liver,kidney,lung and so on of mice after acute inorganic arsenic exposure

目的探讨急性经口无机砷暴露小鼠肝、肾、肺和膀胱中形态砷的动态变化与分布规律。方法将68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(n=4)和2.5、10 mg/kg亚砷酸钠染毒组(n=32)。给予小鼠一次性灌胃方式染毒,染毒容量为10 ml/kg。于染毒后1、3、6、9、12、24、48和72 h,检测肝脏、肾脏、肺脏和膀胱组织中五价无机砷(iAs^5+)、三价无机砷(i As^3+)、单甲基胂酸(MMA)和二甲基胂酸(DMA)含量,并计算总砷(TAs)含量。结果与2.5 mg/kg亚砷酸钠染毒组比较,10 mg/kg亚砷酸钠染毒1~72 h时小鼠肝脏TAs含量、1~24 h小鼠肝脏iAs^3+含量和染毒3 h时小鼠肝脏iAs^5+含量及染毒1~12 h时小鼠肝脏DMA含量均较高,差异均有统计学意义(P<0.05);而不同染毒时间小鼠肝脏MMA含量均无明显改变。且随着染毒时间的延长,小鼠肝脏中TAs及iAs^5+、iAs^5+的含量均呈下降趋势,而DMA呈先升高后下降的趋势。与2.5 mg/kg亚砷酸钠染毒组比较,10 mg/kg亚砷酸钠染毒3、9、12 h时小鼠肾脏TAs、iAs^3+含量和染毒1 h时小鼠肾脏iAs^5+含量及染毒1、3、9、12 h时小鼠肾脏MMA含量以及染毒1、3 h时小鼠肾脏DMA含量均较高,差异均有统计学意义(P<0.05)。且随着染毒时间的延长,小鼠肾脏中TAs及iAs^5+、iAs^3+的含量均呈下降趋势,而MMA和DMA呈先升高后下降的趋势。与2.5 mg/kg亚砷酸钠染毒组比较,10 mg/kg亚砷酸钠染毒1~24 h时小鼠肺脏TAs、iAs^3+、MMA、DMA含量均较高,除染毒6 h时MMA含量及染毒1、3 h时DMA含量外,差异均有统计学意义(P<0.05);而不同染毒时间小鼠肺脏i As^5+含量均无明显改变。且随着染毒时间的延长,小鼠肺脏中iAs^3+的含量均呈下降趋势,而TAs及MMA、DMA呈先升高后下降的趋势。与2.5 mg/kg亚砷酸钠染毒组比较,10 mg/kg亚砷酸钠染毒1~72 h时小鼠膀胱TAs含量、染毒3 h时小鼠膀胱iAs^5+含量和染毒1 h时小鼠膀胱iAs^3+含量及染毒1、6~12 h时小鼠膀胱MMA含量以及染毒1、12~72 h时小鼠肾脏DMA含量均较高,差异均有统计学意义(P<0.05)。结论急性经口无机砷暴露小鼠肝脏和肾脏中TAs、iAs^5+、iAs^3+含量呈时间依赖性下降趋势;肺脏中TAs、MMA、DMA含量随时间变化呈先升高后下降趋势;膀胱中各形态砷时间变化趋势不明显。

Objective To investigate the dynamic changes and distribution pattern of arsenic species in liver,kidney,lung and bladder of mice after a single oral administration of arsenite.Methods A total of 68 healthy Kunming mice(female,eightweek old)were randomly assigned to 17 groups by body weight,which were control group(saline)(n=4),2.5 and 10 mg/kg sodium arsenite(NaAsO2)group(n=32)with eight treatment periods.Mice were treated by an single oral administration of NaAsO2,and the exposure capacity was 10 ml/kg.After NaAsO2 treatment for 1,3,6,9,12,24,48 and 72 h,pentavalent inorganic arsenic(iAs^5+),trivalent inorganic arsenic(iAs^3+),monomethylated arsenic(MMA)and dimethylated arsenic(DMA)in liver,kidney,lung and urinary bladder were determined,then TAs levels were calculated.Results TAs levels in liver of 10 mg/kg NaAsO2-exposed mice treated for 1-72 h,iAs^3+levels in liver of 10 mg/kg NaAsO2-exposed mice treated for 1-24 h,iAs^5+levels in liver of 10 mg/kg NaAsO2-exposed mice treated for 3 h,as well as DMA levels in liver of 10 mg/kg NaAsO2-exposed mice treated for 1-12 h were significantly higher than 2.5 mg/kg NaAsO2 group(P<0.05),while MMA levels were not changed at different time points.With the prolongation of exposure time,the levels of TAs,iAs^5+and iAs^3+in the liver of mice showed a downward trend,while DMA increased first and then decreased.TAs and iAs^3+levels in kidney of 10 mg/kg NaAsO2 group treated for 3,9,12 h,iAs^5+levels in kidney of 10 mg/kg NaAsO2 group treat for 1 h,MMA levels in kidney of 10 mg/kg NaAsO2 group treated for 1,3,9,12 h,and DMA levels in kidney of 10 mg/kg NaAsO2 group treated for 1,3 h were significantly higher than 2.5 mg/kg NaAsO2-exposed group(P<0.05).With the prolongation of exposure time,the contents of TAs,iAs^5+and iAs^3+in the kidney of mice showed a downward trend,while MMA and DMA increased first and then decreased.The levels of TAs,iAs^3+,MMA and DMA in lung of 10 mg/kg NaAsO2-exposed mice treated for 1-24 h were significantly higher than 2.5 mg/kg NaAsO2 group(P<0.05),excluding MMA levels for 6 h and DMA levels for 1,3 h.while iAs^5+levels were not significantly changed at different exposure time points.With the prolongation of exposure time,the levels of TAs,iAs^5+and iAs^3+decreased,while MMA and DMA increased first and then decreased.TAs levels in urinary bladder of 10 mg/kg NaAsO2-exposed mice treated for 1-72 h,iAs^5+levels in urinary bladder of 10 mg/kg NaAsO2-exposed mice treated for 3 h,iAs^3+levels in urinary bladder of 10 mg/kg NaAsO2-exposed mice treated for 1 h,MMA levels in urinary bladder of 10 mg/kg NaAsO2-exposed mice treated for 1 h and 6-12 h,DMA levels in urinary bladder of 10 mg/kg NaAsO2-exposed mice treated for 1 h and 12-72 h were significantly higher than 2.5 mg/kg NaAsO2 group(P<0.05).Conclusion TAs,iAs^5+and iAs^3+levels in liver and kidney of acute inorganic arsenic-orally exposed mice exhibit time-dependent downward trend;TAs,MMA,DMA levels in lung increase first and then decrease over time;While various arsenic species in bladder show no significant changes.