间歇低氧大鼠肝细胞GLUT-2、GCK表达变化与胰岛素抵抗的相关性研究

发布时间：2018-04-06 23:35

本文选题：间歇低氧　切入点：胰岛素抵抗　出处：《山西医科大学》2017年硕士论文

【摘要】：目的:制备间歇低氧大鼠模型,检测肝细胞葡萄糖转运蛋白-2(GLUT-2)、葡萄糖激酶(GCK)蛋白表达量变化及测定胰岛素抵抗的程度,探讨间歇低氧条件下GLUT-2、GCK的表达变化与机体胰岛素抵抗发生的相关机制。方法:24只6周龄健康雄性SD大鼠随机分为对照组(NC组)、间歇低氧4周组(IH4组)和间歇低氧8周组(IH8组),每组8只。造模组按预先设定的通气模式给与间歇低氧暴露(9:00am-5:00pm),对照组给予间歇压缩空气,暴露时间同造模组。测定每组大鼠空腹血糖、空腹胰岛素,稳态模型评估-胰岛素抵抗指数(HOMA-IR)及胰岛素敏感指数(ISI)评估胰岛素抵抗程度。免疫组织化学染色观察肝细胞GLUT-2、GCK蛋白表达变化,测定平均灰度值对蛋白表达进行定量分析,整合数据并统计分析。结果:1.与NC组相比,造模组空腹血糖、空腹胰岛素、HOMA-IR升高,ISI降低,且随暴露时间的延长,上述变化更趋明显,差异有统计学意义(P均0.05)。2.间歇低氧条件下肝细胞GLUT-2、GCK蛋白表达量均降低,与4周组相比8周组变化更显著,差异有统计学意义(P均0.05)。3.Pearson相关分析显示:GLUT-2、GCK平均灰度值均与HOMA-IR呈正相关(r=0.894,r=0.869,P均0.05),与ISI呈负相关(r=-0.886,r=-0.906,P均0.05)。结论:1.间歇低氧暴露组大鼠空腹血糖、空腹胰岛素水平及HOMA-IR升高,ISI降低,机体呈现糖代谢紊乱及胰岛素抵抗征象,且随着暴露的时间延长上述变化趋于明显;2.间歇低氧条件下肝细胞GLUT-2、GCK蛋白表达下调,且两蛋白所测灰度值与HOMA-IR相关;3.肝细胞GLUT-2、GCK蛋白参与间歇低氧条件下肝胰岛素抵抗的发生。
[Abstract]:Objective: to establish a rat model of intermittent hypoxia and to detect the expression of glucose transporter (GLUT-2), glucokinase (GCK) and the degree of insulin resistance (IR) in hepatocytes.To investigate the relationship between the expression of GLUT-2 GCK and insulin resistance under intermittent hypoxia.Methods Twenty four male Sprague-Dawley rats aged 6 weeks were randomly divided into control group (NC group), intermittent hypoxia group (group IH4) and intermittent hypoxia group (group IH8, 8 rats in each group).The model group was given intermittent hypoxia exposure (9: 00am-5: 00pmg) according to the preset ventilation mode, while the control group was given intermittent compressed air. The exposure time was the same as the model group.Fasting blood glucose, fasting insulin, homeostasis model assessment-insulin resistance index (HOMA-IRI) and insulin sensitivity index (ISI) were measured in each group.The expression of GLUT-2 GCK in hepatocytes was observed by immunohistochemical staining. The expression of GLUT-2GCK was quantitatively analyzed by measuring the mean gray value, and the data were integrated and analyzed statistically.The result is 1: 1.Compared with NC group, fasting blood glucose, fasting insulin and HOMA-IR in model group increased and ISI decreased. With the prolongation of exposure time, the above changes were more obvious, and the difference was statistically significant (P < 0.05).Conclusion 1.In intermittent hypoxic exposure group, fasting blood glucose, fasting insulin level and HOMA-IR were increased and decreased, the body showed glucose metabolism disorder and insulin resistance signs, and the above changes tended to be obvious with the prolongation of exposure time.The expression of GLUT-2 GCK protein was down-regulated in hepatocytes under intermittent hypoxia, and the gray values of the two proteins were correlated with HOMA-IR.GLUT-2 GCK protein is involved in the development of insulin resistance in the liver under intermittent hypoxia.
【学位授予单位】：山西医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R587.1;R766

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