李述刚, 徐上知, 牛强, 丁玉松, 马儒林, 闫贻忠, 郭淑霞, 木拉提, 王海霞, 冯刚玲. 三氧化二砷染毒小鼠肝脏中砷甲基化水平与肝脏氧化应激的关系[J]. 环境卫生学杂志, 2015, 5(2): 89-93, 98. DOI: 10.13421/j.cnki.hjwsxzz.2015.02.002
    引用本文: 李述刚, 徐上知, 牛强, 丁玉松, 马儒林, 闫贻忠, 郭淑霞, 木拉提, 王海霞, 冯刚玲. 三氧化二砷染毒小鼠肝脏中砷甲基化水平与肝脏氧化应激的关系[J]. 环境卫生学杂志, 2015, 5(2): 89-93, 98. DOI: 10.13421/j.cnki.hjwsxzz.2015.02.002
    LI Shugang, XU Shangzhi, NIU Qiang, DING Yusong, MA Rulin, YAN Yizhong, GUO Shuxia, MU Lati, WANG Haixia, Feng Gangling. Relationship Between Arsenic Methylation and Oxidative Stress in Mice Liver Induced by Arsenic Trioxide[J]. Journal of Environmental Hygiene, 2015, 5(2): 89-93, 98. DOI: 10.13421/j.cnki.hjwsxzz.2015.02.002
    Citation: LI Shugang, XU Shangzhi, NIU Qiang, DING Yusong, MA Rulin, YAN Yizhong, GUO Shuxia, MU Lati, WANG Haixia, Feng Gangling. Relationship Between Arsenic Methylation and Oxidative Stress in Mice Liver Induced by Arsenic Trioxide[J]. Journal of Environmental Hygiene, 2015, 5(2): 89-93, 98. DOI: 10.13421/j.cnki.hjwsxzz.2015.02.002

    三氧化二砷染毒小鼠肝脏中砷甲基化水平与肝脏氧化应激的关系

    Relationship Between Arsenic Methylation and Oxidative Stress in Mice Liver Induced by Arsenic Trioxide

    • 摘要:
      目的 探讨三氧化二砷(As2O3)染毒小鼠肝脏组织中砷甲基化水平的变化及其与肝脏氧化应激关系, 为揭示砷甲基化水平在砷毒性机制中的作用提供依据。
      方法 将40只昆明种小鼠随机分为对照组(0.9%生理盐水)、As2O3低中高剂量组(1.0、2.0和4.0 mg/kg)组, 连续灌胃5周; 采用高效液相色谱与原子荧光联用技术(HPLC-HGAFS)测定肝脏组织中三价无机砷(As3+)、五价无机砷(As5+)、一甲基胂(MMA)、二甲基胂(DMA)含量及构成比(%), 计算砷一甲基化指数(PMI)、二甲基化指数(SMI); 利用试剂盒测定丙二醛(MDA)、谷胱甘肽(GSH)、超氧化物歧化酶(SOD)、总抗氧化能力(T-AOC)。
      结果 随着As2O3剂量增加, 小鼠肝脏组织中各形态砷代谢产物含量增加(P<0.001), 砷甲基化水平(iAs%、MMA%、DMA%、PMI、SMI)提高(P<0.001);小鼠肝脏MDA显著高于对照组(P<0.001), GSH、SOD、T-AOC显著低于对照组(P<0.001);1 mg/kg染毒剂量时, PMI与T-AOC呈负相关(P<0.05), SMI与GSH、SOD呈负相关(P<0.05);在2 mg/kg染毒剂量时, PMI、SMI与MDA呈正相关(P<0.05) 而与GSH、SOD呈负相关(P<0.05);在4 mg/kg染毒剂量时, PMI与MDA呈正相关(P<0.05), PMI、SMI与GSH、SOD呈负相关(P<0.05)。
      结论 随着砷染毒剂量的增加, 小鼠肝脏组织中各种形态砷含量增多, 砷甲基化水平提高, 进而导致小鼠肝脏氧化损伤严重。

       

      Abstract:
      Objective To investigate the relationship between arsenic methylation and oxidative stress in the liver of mice induced by arsenic trioxide(As2O3).
      Methods Forty healthy KM mice were randomly divided into a control group(0.9% saline) and three arsenic groups treated with As2O3(1.0, 2.0 and 4.0 mg/kg) by gastric perfusion for 5weeks. The content of inorganic arsenics(As3+ and As5+), mono-methyl arsine(MMA) and dimethyl arsine(DMA) in liver were determined by high efficiency liquid chromatography and hydride genesis atomic fluorescence spectroscopy (HPLC-HGAFS) and the proportion of the those were calculated.The indexes of arsenic methylation including PMI and SMI were calculated. The activity of SOD and the levels of MDA, GSH and T-AOC were tested by kits.
      Results With increasing the treated dosage of As2O3, the contents of arsenic metabolites and arsenic methylation in liver were significantly increased(P < 0.001). The level of MDA in the arsenic groups was significantly higher than that in the control group(P < 0.001), while the levels of GSH, SOD and T-AOC were lower significantly than the control group(P < 0.001). In the 1mg/kg As2O3 group, PMI was negatively correlated with T-AOC(P < 0.05), SMI was also negatively correlated with GSH and SOD(P < 0.05). In the 2 mg/kg As2O3 group, both PMI and SMI were positively correlated with MDA(P < 0.05), while negatively correlated with GSH and SOD(P < 0.05). In the 4 mg/kg As2O3 group, PMI was positively correlated with MDA(P < 0.05), while PMI and SMI were negatively correlated with GSH and SOD(P < 0.05).
      Conclusion The arsenic methylation in liver was increased with higher treated dosage of arsenic trioxide, which might aggravate the oxidative stress of liver in mice.

       

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