四溴二苯醚对小鼠胰岛素敏感性及胰岛形态与功能的影响
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江苏省医学重点学科资助(SK200214),江苏省医学重点人才资助和江苏省医学领军人才资助(RC2002047,LJ200619)


Effects of BDE-47 on the function and morphology of pancreatic islets and insulin sensitivity of mice
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    目的:研究环境内分泌干扰物四溴二苯醚(BDE-47)对胰岛素敏感性及胰岛形态与功能的影响-方法:雄性ICR小鼠随机分为A组(空白对照组)-B组(BDE-47,25 μg/kg组)-C组(BDE-47,50 μg/kg组)和D组(E2,50 μg/kg组)-实验周期为4周-分别行腹腔葡萄糖耐量实验(IPGTT)和胰岛素耐量实验(ITT)评估胰岛素敏感性及胰岛功能;通过免疫组化对胰岛进行形态与量化分析-结果:基础状态下,各组小鼠空腹血糖与葡萄糖耐量均无异常;BDE-47作用后,与正常对照组相比,空腹血糖及胰岛素水平无明显变化-但葡萄糖负荷后C组小鼠血糖峰值显著降低,曲线下面积减小,而胰岛素释放峰值明显增高,胰岛素曲线下面积明显变大-另一方面,胰岛素负荷后,各组小鼠血糖变化趋势基本一致-与A组相比,B组和C组小鼠胰岛素抵抗指数和胰岛素敏感指数均未见明显差异-C组小鼠胰腺组织中胰岛的胰岛素染色阳性区域平均光密度-胰岛素相对浓度(IRC)-胰岛素阳性表达细胞面积等指标均明显高于其他各组-结论:低浓度四溴二苯醚导致小鼠葡萄糖负荷下胰岛素释放量明显增多,提示环境内分泌干扰物可促使胰岛内胰岛素容量增加,并最终导致高胰岛素血症-

    Abstract:

    Objective:To investigate the effect of 2,2′,4,4′-tetrabromodiphenyl ether(BDE-47) on the function and morphology of pancreatic islets and insulin sensitivity in vivo. Methods:Male mice were randomly divided into group A(normal control), group B(BDE-47-treated group,25 μg/kg), group C(BDE-47-treated group,50 μg/kg) and group D(E2-treated group,50 μg/kg). The observation time was four weeks after exposure to BDE-47. The intraperitoneal glucose tolerance test and insulin tolerance test were performed to evaluate the function of pancreatic islets and insulin sensitivity,respectively. Immunohistochemistry technique was used to measure the changes of islet morphology and quantity of mice. Results:Fasting blood glucose and glucose tolerance of the mouse were both normal on basic state. Compared with group A,the levels of fasting glucose and fasting insulin were not significantly different in group B and C after the injection of BDE-47. The peak of blood glucose level and the area under the curve(AUC) were all decreased statistically after the glucose load in group C,and the peak of insulin secretion and the AUC were both increased dramatically. No alteration of blood glucose level was found in the mice of group B and group C after insulin injection,suggesting normal insulin sensitivity. There was no statistical difference in both insulin resistance index and insulin sensitive index among three groups. The average photo-density of insulin-expression positive zone,insulin relative concentration(IRC),insulin-expression positive cell area were all increased significantly in group C. Conclusion:Low concentration of BDE-47 insulin secretion of the mouse caused elevate after glucose load,indicating that environmental endocrine disruptors play an important role in the increase of insulin content of islets and the induction of hyperinsulinemia.

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王 科,刘翠萍,茅晓东,徐宽枫,钱春花,刘 超.四溴二苯醚对小鼠胰岛素敏感性及胰岛形态与功能的影响[J].南京医科大学学报(自然科学版),2008,28(11):1415-1420

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  • 收稿日期:2008-05-08
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