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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(i As%、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。
Objective To investigate the changes of arsenic methylation level and liver oxidative stress in arsenic trioxide (As 2 O 3) -induced mice, and provide basis for revealing the role of arsenic methylation in arsenic toxicity mechanism. Methods Forty Kunming mice were randomly divided into control group (0.9% saline), low, medium and high dose As2O3 (1.0, 2.0 and 4.0 mg / kg) groups for continuous 5 weeks. High performance liquid chromatography The content of As3 +, As5 +, MMA and DMA in liver tissue were determined by HPLC-HGAFS. The contents of As3 + ), Calculated arsenic methylation index (PMI), dimethylation index (SMI); measured by using the kit MDA, GSH, SOD, Total antioxidant capacity (T-AOC). Results As As2O3 dose increased, the content of arsenic metabolites increased (P <0.001) and arsenic methylation (MMA%, DMA%, PMI, SMI) (P <0.001). The levels of GSH, SOD and T-AOC were significantly lower than those of the control group (P <0.001). At the dose of 1 mg / kg, PMI and T-AOC (P <0.05). There was a negative correlation between SMI and GSH and SOD (P <0.05). At the dose of 2 mg / kg, there was a positive correlation between PMI and SMI and MDA (P <0.05). At the dose of 4 mg / kg, there was a positive correlation between PMI and MDA (P <0.05). PMI and SMI were negatively correlated with GSH and SOD (P <0.05). Conclusion With the increase of dose of arsenic, the various forms of arsenic in liver tissue of mice increased, the arsenic methylation level increased, which led to severe oxidative damage in mouse liver.