目的三价无机砷通过细胞膜上的水甘油通道蛋白质转运进入细胞内,本研究探讨锌离子对细胞和组织吸收三价无机砷的作用。方法 32只雄性ICR小鼠随机分为4组(8只/组),灌胃给予ICR小鼠10 mg/kg三氧化二砷前15 min灌胃给予不同浓度的硫酸锌(浓度分别为0、25、50和100 mg/kg)。给予三氧化二砷2 h后,取小鼠肝脏、肾脏、心脏、肺、皮肤和睾丸等组织经硝酸消化后,原子荧光光谱法测定组织中砷含量。培养Raw 264.7细胞,按染毒剂量分为4组:对照组、砷暴露组(iAs^3+10μmol/L)、砷和锌联合暴露组(iAs^3+10μmol/L+Zn^2+10μmol/L、iAs^3+10μmol/L+Zn^2+50μmol/L),利用细胞MTT实验检测细胞活性变化。结果给予小鼠50或100 mg/kg硫酸锌和10 mg/kg三氧化二砷后,与仅给予三氧化二砷小鼠相比,肝脏、肾脏、心脏、睾丸和皮肤组织中砷含量明显减低,而低剂量硫酸锌(25 mg/kg)对小鼠组织中砷含量没有影响。不管给予硫酸锌剂量的高低,肺组织中砷含量均没有明显改变。Raw 264.7细胞培养基中加入10和50μmol/L硫酸锌后,砷对细胞的毒性明显降低。结论二价锌离子能抑制多个组织吸收三价无机砷,从而使组织中砷含量降低;二价锌离子也能降低三价无机砷对Raw 264.7细胞的毒性。
Objective Trivalent inorganic arsenic[iAs^3+]is transported into cells by aquaglyceroporins in the cell membrane,this study investigated the effect of Zn^2+ on the uptake of iAs^3+by tissues of mice and cells. Methods 32 male mice were divided into four groups randomly( 8 /group),the four groups were treated with different does of 0 mg·kg^-1,25 mg·kg^-1,50 mg·kg^-1,100 mg·kg^-1 zinc sulphate by intragastric administration,respectively. After 15 minutes,they were all administered 10 mg·kg^-1 iAs^3+ by intragastric administration. 2 hours later,mice tissues( liver,kidney,heart,lung,skin,testis and so on) were digested by nitric acid and measured the concentration of arsenic in tissues by atomic fluorescence spectrometer. Raw 264. 7 cells were designed into four groups( control,10 μmol /L iAs^3+,10 μmol/L iAs^3++ 10 μmol /L Zn^2+,10 μmol/L iAs^3++ 50 μmol /L Zn^2+),MTT assay was used to detect the toxicity of cells. Results The levels of arsenic in liver,kidney,heart,testis and skin were decreased significantly after treatment with 50 mg·kg^-1 and 100 mg·kg^-1Zn^2+ compared with mice treated with iAs^3+only,but the level of arsenic in the lung were no difference among four groups. After Raw 264. 7 cells cocultured with 10μmol/L or 50 μmol/L Zn^2+,the toxicity of iAs^3+on cells was decreased. Conclusion Zn^2+ may inhibit the uptake of iAs^3+ in tissues of mice,and decreased the levels of As in tissues. Zn^2+also lowered the cytotoxicity of iAs2 +in Raw 264. 7 cells.