三氧化二砷染毒小鼠肝功能及砷甲基化水平变化

发布时间：2019-03-21 09:47

【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功能损伤的关系,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(i As3+)、五价无机砷(i As5+)、一甲基胂(MMA)、二甲基胂(DMA)含量,并计算砷一甲基化指数(PMI)、二甲基化指数(SMI);利用试剂盒测定天冬氨酸转酶(AST)与丙氨酸转氨酶(ALT)活力。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(P0.001),砷甲基化水平(i As%、MMA%、PMI、SMI)提高(P0.001);小鼠肝脏系数、ALT、AST显著高于对照组(P0.001);在1 mg/kg染毒剂量时,MMA%与ALT、AST呈负相关(rALT=-0.667,PALT=0.005;rAST=-0.649,PAST=0.042),DMA%与ALT呈正相关(r=0.742,P=0.014),SMI与ALT、AST呈正相关(rALT=0.672,rAST=0.649,P0.05)。结论随着砷染毒剂量的增加,小鼠肝脏组织中各种形态砷蓄积增多,砷甲基化水平提高,转氨酶活性升高,致小鼠肝功能损伤。
[Abstract]:Aim to investigate the changes of arsenic methylation level in the liver of mice exposed to arsenic trioxide (As2O3) and the relationship between arsenic methylation level and liver function damage, so as to provide a basis for revealing the role of arsenic methylation level in the mechanism of arsenic toxicity. Methods 40 Kunming mice were randomly divided into three groups: control group (0.9% saline), As2O3 low, medium and high dose group (1.0,2.0 and 4.0 mg/kg). The contents of trivalent inorganic arsenic (I As3), pentavalent inorganic arsenic (I As5) and monomethylarsine (MMA), dimethylarsine (DMA) in liver tissue were determined by high performance liquid chromatography and atomic fluorescence spectrometry (HPLC-HGAFS). The arsenic-methylation index (PMI),) was calculated, and the (SMI); (as-methylation index) was calculated. The activities of aspartate transaminase (AST) and alanine aminotransferase (ALT) were measured with a kit. Results with the increase of the dose of As2O3, the contents of arsenic metabolites and the level of arsenic methylation (I-As%,MMA%,PMI,SMI) in the liver tissue of mice increased (P0.001) and the level of arsenic methylation (I-As%,MMA%,PMI,SMI) increased (P0.001). The liver coefficient and ALT,AST in mice were significantly higher than those in control group (P0.001), and there was a negative correlation between MMA% and ALT,AST at 1 mg/kg dose (rALT=-0.667,PALT=0.005;). There was a positive correlation between rAST=-0.649,PAST=0.042, DMA% and ALT (r = 0.742, P = 0.014), SMI and ALT,AST) (rALT=0.672,rAST=0.649,P0.05). Conclusion with the increase of arsenic exposure dose, the accumulation of various forms of arsenic in the liver tissue of mice increased, the level of arsenic methylation increased, the activity of transaminase increased, and the liver function of mice was damaged.
【作者单位】：石河子大学医学院预防医学系;新疆生产建设兵团第四师疾病预防控制中心;
【基金】：石河子大学高层次人才项目(RCZX201112) 兵团重点领域科技攻关项目(2014BA039)
【分类号】：R114

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