【摘要】 目的 探讨微小RNA-155(miR-155)在亚砷酸钠诱导肝胰岛素抵抗中的作用，为研究慢性砷暴露所致糖尿病的分子机制及发现早期生物标志物提供科学依据。方法 将48只SPF级5周龄C57BL/6J雄性小鼠按体重将小鼠随机分4组，分别为对照组和0.5、5、50 mg/L亚砷酸钠染毒组，每组12只。采用自由饮水方式进行染毒，持续48周。进行葡萄糖耐量试验和胰岛素耐量试验；检测小鼠肝脏中miR-155水平及总蛋白PPAR-γ、膜蛋白和浆蛋白中GLUT4水平。结果 与对照组相比，各浓度亚砷酸钠染毒组小鼠腹腔分别注射葡萄糖2 h后和胰岛素1 h后AUC均升高，差异均有统计学意义（P<0.05）；且随着亚砷酸钠染毒浓度的升高，小鼠血糖AUC均呈上升趋势。与对照组比较，5、50 mg/L亚砷酸钠染毒组小鼠肝脏组织中miR-155的表达水平均升高，差异有统计学意义（P<0.05）；且随着亚砷酸钠染毒浓度的升高，小鼠肝脏组织中miR-155的表达水平呈上升趋势。与对照组相比，5、50 mg/L亚砷酸钠染毒组小鼠肝脏组织中PPAR-γ蛋白及肝脏膜蛋白GLUT4的表达水平均降低，差异有统计学意义（P<0.05）；且随着亚砷酸钠染毒浓度的升高，小鼠肝脏组织中PPAR-γ蛋白及肝脏膜蛋白GLUT4的表达水平均呈下降趋势。结论 慢性砷暴露使小鼠葡萄糖耐量受损和胰岛素敏感性下降，肝脏结构和功能受损，引起miR-155水平升高，PPAR-γ和膜蛋白GLUT4水平降低，从而诱导肝胰岛素抵抗。更多还原

【Abstract】 Objective To understand the role of microRNA-155（miR-155） in the induction of hepatic insulin resistance induced by sodium arsenite（NaAsO₂）,and provide scientific basis for the study of the molecular mechanism of chronic arsenic exposure induced diabetes and the discovery of early biomarkers. Methods Totally 48 male C57BL/6J mice were randomly divided into four groups,12 in each,and exposed to sodium arsenite through drinking water at the doses of 0,0.5,5,and 50mg/L respectively for 48 consecutive weeks. Glucose and insulin tolerance tests were conducted,and the liver structure and functional damage of the mice were observed after sacrificed,and miR-155 levels and total protein PPAR-γ in the liver,GLUT4 levels in membrane proteins and plasma proteins were determined. Results Compared with the control group,the area under the curve of blood glucose changes with time in mice exposed to sodium arsenite of various concentrations after intraperitoneal injection of glucose for 2 h and insulin for 1 h was significantly higher（P<0.05）. Compared With the control group,the expression level of miR-155 in liver tissue of mice exposed to 5 mg/L and 50 mg/L sodium arsenite significantly increased（P<0.05）,with a dose dependent manner. Compared with the control group,the expression levels of PPAR-γ protein and liver membrane protein GLUT4 in the liver tissue of mice treated with 5 mg/L and 50 mg/L sodium arsenite significantly decreased（P<0.05）,with a dose dependent manner. Conclusion Chronic arsenic exposure can cause glucose tolerance and insulin sensitivity impaired,liver structure and function damaged,and miR-155 levels increased,the levels of PPAR-γ and membrane protein GLUT4 decreased,thereby inducing hepatic insulin resistance.更多还原