• 关键词：砷  葡萄糖耐量  TNF-α  IRS2  GLUT2  葡萄糖稳态

• 基金项目：国家自然科学基金（No.31500504，31371868）；山西省重点研发计划社会发展项目（No.201703D321026-4）；山西省优秀人才科技创新项目（No.201605D211031）

• 曾群
• 1. 山西大学生命科学学院, 环境科学研究所, 太原 030006;2. 山西中医药大学基础医学院, 太原 030024

• 仪慧兰
• 山西大学生命科学学院, 环境科学研究所, 太原 030006

• 黄立群
• 中国辐射防护研究院, 太原 030006

• 安全
• 中国辐射防护研究院, 太原 030006

• 摘要：通过饮水亚砷酸钠（NaAsO₂）暴露，研究了砷对小鼠葡萄糖稳态的影响及相关作用机制.结果发现，C57BL/6小鼠经饮水暴露5、50 mg·L^-1 As 6个月，每月空腹血糖和1~4个月内葡萄糖耐量与对照组无明显变化.砷暴露5、6个月导致葡萄糖耐量受损且具有剂量和时间依赖性，与此同时，血清丙氨酸转氨酶（ALT）和天冬氨酸转氨酶（AST）活性在5 mg·L^-1 As组无明显改变，但50 mg·L^-1 As组显著高于对照组；苏木精和伊红（HE）染色观察到砷暴露组小鼠肝脏结构损伤，炎性细胞浸润.此外，砷暴露组肝脏中促炎症因子肿瘤坏死因子（TNF-α） mRNA水平显著上升，胰岛素受体底物（IRS2）和葡萄糖转运蛋白（GLUT2） mRNA转录水平下降，高剂量砷组基因表达的增减幅度较大.研究结果表明，长期砷暴露会引发实验动物葡萄糖耐量受损、肝脏功能和结构损伤，葡萄糖耐量受损可能与砷暴露组胰岛素受体后信号转导障碍和肝脏葡萄糖转运异常有关.

• Abstract：In the present study, we aimed to study the effect of arsenic (As) on glucose homeostasis and the underlying mechanisms. C57BL/6 mice were treated with 5 and 50 mg·L^-1 As for 6 months via drinking water. The results showed that no significant difference was observed in fasting blood glucose monthly and the glucose tolerance during 1~4 months of As exposure. However, As markedly reduced the glucose tolerance in a concentration- and time-dependent manner after 5 and 6 months, respectively. Meanwhile, no significant difference was found in activities of serum alanine transaminase (ALT) and aspartate transaminase (AST) in mice exposed to 5 mg·L^-1 As, but, activities of serum ALT and AST significantly increased in mice exposed to 50 mg·L^-1 As. By using Hematoxylin-eosin (HE) staining, liver structure damage and inflammatory cells infiltration were obviously observed at both As-treated groups. In addition, the transcript levels of tumor necrosis factor-α (TNF-α) increased significantly, while mRNA levels of insulin receptor substrate 2 (IRS2) and glucose transporter 2 (GLUT2) decreased in mouse livers. The changes of the gene expression levels in high dose of As group were larger than that in low dose of As group. These results showed that long-term As exposure could lead to the impaired glucose tolerance, together with the liver function and structure damage in experimental animals. The impaired glucose tolerance might be correlated with the disorder of insulin post-receptor signaling transduction and abnormal glucose transportation in liver.

• Key words：arsenic  glucose tolerance  TNF-α  IRS2  GLUT2  glucose homeostasis

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