亚硒酸钠对糖尿病肾病大鼠肾脏脂联素表达的影响
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重庆市卫生局课题(07-1-076).


Influence of sodium selenite on adiponectin expression in kidney of rats with diabetic nephropathy
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Supported by Chongqing Municipal Health Bureau(07-1-076).

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    摘要:

    目的:探讨亚硒酸钠对糖尿病肾病大鼠肾脏脂联素表达的影响及二者间的关系,从而研究亚硒酸钠和脂联素在糖尿病肾病中的作用机制。 方法:通过链脲佐菌素法并给予高脂饮食诱导模拟大鼠糖尿病肾病模型,实验设空白对照组、糖尿病肾病对照组、亚硒酸钠干预组,每组10只。亚硒酸钠干预组每日给予亚硒酸钠溶液1 μg/kg灌胃,其他各组给予等量盐水溶液灌胃。灌胃10周后处死大鼠,取大鼠血、尿标本测相关生化指标。快速切取小块肾皮质组织,4%戊二醛固定,制电镜切片扫描电镜观察超微结构。取肾脏组织标本制石蜡切片光镜下观察病理改变及免疫组化分析定位蛋白表达,定量PCR法检测脂联素的mRNA表达、蛋白质印迹法检测脂联素蛋白表达。结果:亚硒酸钠干预组大鼠基本状况和生化指标较糖尿病肾病对照组明显改善,光镜下亚硒酸钠干预组病理改变和电镜下超微结构较糖尿病肾病对照组明显减轻。免疫组化分析,亚硒酸钠干预组脂联素蛋白着色较糖尿病肾病对照组明显增强,且肾小管、肾小球内均有着色。亚硒酸钠干预组脂联素mRNA是空白对照组的2.043倍,糖尿病肾病对照组脂联素mRNA是空白对照组的1.373倍。亚硒酸钠干预组脂联素蛋白表达水平高于糖尿病肾病对照组及空白对照组,差异有统计学意义(P<0.05)。结论:亚硒酸钠通过抗氧化应激、增加外周组织对胰岛素的敏感性从而促进肾脏脂联素表达,表明亚硒酸钠和脂联素在延缓和防治糖尿病肾病的发生发展中可能起重要作用。

    Abstract:

    Objective:To investigate the influence of sodium selenite on adiponectin expression in kidney of rats with diabetic nephropathy and the relation between sodium selenite and adiponectin,so as to investigate the role of sodium selenite and adiponectin in diabetic nephropathy.Methods: Diabetic nephropathy rat models were established by injecting streptozocin intraperitoneally and high fat diet.The study was divided into 3 groups,namely,a control group,a diabetic nephropathy group and a selenite-treated group.Animals in the selenite-treated group were given selenite solution 1 μg/kg daily via intragastric administration; those in the other 2 groups were given the same dose of saline in the same way.The animals were sacrificed 10 weeks later and the blood and urine samples were used for biochemical examination.Samples of renal cortex were cut quickly and fixed with 4% glutaral for observation under scanning electron microscope.The renal samples were made into paraffin section for observation of the pathological changes under light microscope and for location of protein expression via immunohistochemistry analysis.The expression of adiponectin mRNA and protein was examined by real-time PCR and Western blotting,respectively.Results: The general condition and biochemical parameters of animals in the selenite-treated group were obviously improved and the pathological changes were obviously releived compared with those in the diabetic nephropathy group.Immunohistochemistry analysis showed that the expression of adiponection in the selenite-treated group was obviously stronger than that in the diabetic nephropathy group,and the expression was found in both glomcrulus and renal tubule.The expression of adiponectin mRNA in the selenite-treated group and diabetic nephropathy group was 2.043 and 1.373 folds that of the control group,respectively.The expression of adiponectin protein in the selenite-treated group was significantly higher than those in the control group and diabetic nephropathy group (P<0.05).Conclusion: Sodium selenite can enhance renal expression of adiponectin through anti-oxidative stress and promotion of periphery tissue sensitivity to insulin,indicating that sodium selenite and adiponectin may play important roles in delaying the progression of diabetic nephropathy.

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  • 收稿日期:2008-12-01
  • 最后修改日期:2009-06-05
  • 录用日期:2009-06-19
  • 在线发布日期: 2009-07-16
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