【作者】 刘霞；

【导师】 曾凡星；

【作者基本信息】 北京体育大学 ， 运动人体科学， 2007， 博士

【摘要】 目的:探讨低氧暴露与运动对肌糖原合成的调节机理,以胰岛素调节肌糖原合成的信号途径作为研究主线,并对低氧暴露与运动调节葡萄糖转运的另一个重要信号途径AMPK进行研究。同时对影响肌糖原合成的下游信号—葡萄糖转运载体4(GLUT4)和糖原生成素(GN)进行研究。方法:以SD雄性大鼠为研究对象,将其分为安静对照组、低氧暴露组、常氧运动组和高住低训组,运动方式为跑台运动,坡度为5度,跑速为20米/分,每周6天,共4周。晚上在氧浓度13.6%的低氧帐篷内低氧暴露12小时,共4周。分别于实验1天、7天、28天和复氧7天取材。观察胰岛β细胞形态与分泌功能、测定骨骼肌胰岛素受体亲和力、探讨调节肌糖原合成的信号通路PI-3K、AMPK、GLUT4和GN蛋白或基因表达在低氧与运动中的变化。结果:(1)间歇性低氧暴露和高住低训在初期,胰腺腺泡在形态上有明显到中度脂肪变性,但随着低氧暴露时间的延长,腺泡脂肪变性减轻。(2)图像分析表明,运动可使胰岛β细胞数量增加,β细胞/胰岛面积百分比增加,而低氧暴露和高住低训则使之减少。(3)从I/G与C/G比值可见,常氧运动和高住低训无显著性差异。(4)低氧和/或运动对胰岛素低亲和力受体的影响更加显著,体现在胰岛素受体亲和力下降,但胰岛素受体结合容量非常显著性增加。(5)常氧运动和高住低训增加骨骼肌肌糖原的含量,且常氧运动更为显著。(6)低氧和/或运动能够增加骨骼肌AMPK和PI3K蛋白的含量,且7天组AMPK和28天组PI3K蛋白含量的增加更为显著。(7)低氧和/或运动能够增加GLUT4mRNA和GNmRNA的表达,且28天组二者增加更为显著。结论:(1)低氧导致胰腺腺泡脂肪变性,但低氧和/或运动均未明显改变胰岛β细胞的正常分泌功能。(2)低氧和/或运动诱导或增强了胰岛素低亲和力受体的密度,说明胰岛素对低氧和/或运动的反应能力增强。(3)低氧和/或运动能够增加骨骼肌肌糖原的含量,但常氧运动更有利于肌糖原的合成。其机理是:一方面通过改变骨骼肌胰岛素受体亲和力及其结合容量、增加骨骼肌PI3K蛋白含量,增强了胰岛素信号途径的作用;另一方面也通过增加AMPK蛋白含量来促进葡萄糖转运。同时低氧和/或运动能够增加GLUT4mRNA和GNmRNA的表达,这对于低氧和/或运动促进骨骼肌肌糖原合成起着重要的作用。更多还原

【Abstract】 Purpose:The purpose of this study was to explore the regulating mechanism of hypoxia exposure and exercise on muscle glycogen synthesis.The main study was the signaling pathway of insulin regulating muscle glycogen synthesis,and we researched on AMPK which was also an important signaling way of regulating glucose transport.Meanwhile, their downstream signals-GLUT4 and GN were studied.Methods:As the subjects of this study,male Sprague-Dawley rats were divided into four groups:Control group,Hypoxia exposure group,Exerxise group and Living high training low(HiLo) group.The mode of exercise was to run on the treadmill,The grade of which was 5,and the speed was 20m/min, lasting for 6 days every week.At night,Hypoxia exposure and HiLo group were exposured in normobaric hypoxic tent where the concentration of oxygen was 13.6%for 12 hours.All these had been lasting 4 weeks,then the rats of each group were killed after the experiment lasting lday, 7days,28days and 35days(7days after restored normal oxygen),and the sample were collected.We observed and analysed the shape and function of pancreas beta cells,measured the affinity of insulin receptors and explored the mRNA and protein expression changes of PI3K,AMPK,GLUT4 and GN which regulated muscle glycogen synthesis in the hypoxia exposure and exercise.Results:(1) The pancreas cells of Hypoxia exposure and HiLo,were obviously and moderately degenerated with adipic shape at lday and 7days after experiment.As the experiment were prolonged,the degeneration were to be lessen.(2) The results of image analysis indicated:exercise increased the numbers of pancreas beta cells,the percentage of beta cells and the area of pancreas were also increased.But all these of Hypoxia exposure and HiLo group were decreased.(3) As the ratio of I/G and C/G, we observed that there was no difference between exercise and HiLo.(4) The effects of hypoxia and/or exercise on insulin receptor of low affinity were more noticeable,hypoxia and/or exercise decreased the affinity of insulin receptor,but obviously increased the number of insulin receptor. (5) Hypoxia and/or exercise increased the content of muscle glycogen, and exercise increased more obviously.(6) Hypoxia and/or exercise increased the protein of AMPK and PI3k,and the protein of AMPK of 7days group and the protein of PI3k of 28 days group increased more obviously. (7) Hypoxia and/or exercise increased the gene expression of GLUT4 and GN,and which of the 28 days groups,were increased more obviously.Conclusions:(1) Hypoxia made the pancreas cells degenerated with adipic shape,,but hypoxia and /or exercise did not obviously change the endocrine fuction of pancreas beta cells.(2) Hypoxia and /or exercise induced or increased the numbers of insulin receptor,which indicated that the responses of insulin to hypoxia and /or exercise were enhanced. (3) Hypoxia and/or exercise increased the content of muscle glycogen,and exercise increased more obviously.The mechanism of which included two signaling way:one was through changing the affinity and the numbers of insulin receptor,increasing the protein of PI3K,and then enhancing the action of insulin signaling pathway;the other was through increasing the protein of AMPK which promoted glucose transport.Moreover hypoxia and/or exercise also increased the gene expression of GLUT4 and GN,which played important roles on promoting muscle glycogen synthesis of hypoxia and/or exercise.更多还原