摘要目的 检测葡萄糖转运蛋白-2(GLUT-2)、葡萄糖激酶(GCK)在间歇低氧大鼠模型肝细胞中表达的变化,探讨间歇低氧引起胰岛素抵抗的相关机制.方法 24只6周龄健康雄性SpragueDawley(SD)大鼠按照随机数字表法分为对照组、间歇低氧4周组(IH4组)和间歇低氧8周组(IH8组),每组8只.间歇低氧组按预设通气模式每天给予间歇低氧暴露8h,对照组给予间歇压缩空气,暴露时间同IH4组.实验结束后测定各组大鼠空腹血糖、空腹胰岛素,计算稳态模型评估-胰岛素抵抗指数(HOMA-IR)及胰岛素敏感性指数(ISI).免疫组织化学染色观察肝细胞GLUT-2、GCK蛋白表达变化,并利用平均灰度值对蛋白进行定量分析.结果 与对照组相比,IH4组及IH8组空腹血糖、空腹胰岛素、HOMA-IR均升高,ISI均降低,且IH8组更明显(F=161.92、51.46、126.99、83.87,P均＜0.05).与对照组相比,IH4组及I-H8组肝细胞GLUT-2、GCK蛋白表达均降低,且IH8组更显著(F=184.91、240.85,P均＜0.05).Pearson相关分析显示,GLUT-2、GCK平均灰度值与ISI呈负相关(r=-0.886、-0.906,P均＜0.05),与HOMA-tR呈正相关(r=0.894、0.869,P均＜0.05).结论 间歇低氧暴露使大鼠肝细胞GLUT-2、GCK蛋白表达下调,可能参与间歇低氧条件下胰岛素抵抗的发生.

abstractsObjective To determine the expression of glucose transporter-2 (GLUT-2) and glucokinase (GCK) in hepatocytes of intermittent hypoxic rat model,and explore the possible mechanisms of insulin resistance caused by intermittent hypoxia.Methods Twenty-four healthy male Sprague-Dawley SD) rats at 6-week age were divided into control group (NC group),4 weeks of intermittent hypoxia group IH4 group) and 8 weeks of intermittent hypoxia group (IH8 group) according to the random number table,with 8 rats in each group.According to the preset ventilation mode,rats in intermittent groups were exposed in intermittent hypoxia for 8 hours every day,whereas rats in NC group were exposed in intermittent com pressed air for the same time with IH4 group.Fasting blood glucose and fasting insulin were tested after experiment;homeostasis model assessment-insulin resistance index (HOMA-IR) and insulin sensitivity index (ISI) were calculated.The expression of hepatic GLUT-2 and GCK protein were measured by immunohistochemical method,and were quantitatively analyzed by the average gray value.Results Compared with NC group,fasting blood glucose,fasting insulin and HOMA-IR were increased,whereas ISI were decreased in IH4 group and IH8 group,especially in IH8 group (F =161.92,51.46,126.99,83.87,all P ＜ 0.05).Compared with NC group,the expression of GLUT-2 and GCK in hepatic cells were decreased in IH4 group and IH8 group,especially in IH8 group (F =184.91,240.85,all P ＜0.05).Pearson correlation analysis showed that the level of GLUT-2 and GCK were negatively correlated with ISI (r =-0.886,-0.906,all P ＜ 0.05),and positively correlated with HOMA-IR (r =0.894,0.869,all P ＜ 0.05).Conclusion Intermittent hypoxia decreases the expression of GLUT-2 and GCK,which may participate in the occurrenee of insulin resistance under the condition of intermittent hypoxia.