慢性间歇性低氧对大鼠肾脏葡萄糖转运蛋白2及胰岛素受体底物2表达的影响

发布时间：2018-06-04 11:28

  本文选题：慢性间歇性低氧 + 胰岛素抵抗　； 参考：《重庆医科大学》2017年硕士论文

【摘要】：目的:睡眠呼吸疾病(Sleep-disordered breathing,SDB)在近几年的研究中发现与全身各种疾病有着密切关系。在临床上最为常见的是阻塞性睡眠呼吸暂停低通气综合征(Obstructive sleep apnea hypopnea syndrome,OSAHS)表现为在睡眠状态下出现的频繁的呼吸不畅或者呼吸暂停,机体在睡眠中反复出现间歇性缺氧导致全身多个系统、多个器官的损害。根据OSAHS的病理生理特征建立一个符合其特征的慢性间歇性低氧实验动物模型,为研究睡眠呼吸疾病提供一个可靠的实验平台。通过建立慢性间歇性低氧及复氧的动物模型,探讨慢性间歇性低氧所致的脂肪因子以及复氧对大鼠糖代谢及肾脏葡萄糖转运蛋白2(GLUT-2)、胰岛素受体底物2(IRS-2)表达的影响。方法:将24只SD雄性成年大鼠随机分为对照组(control),慢性间歇性低氧组(CIH),复氧组(RH)。CIH组和RH组在慢性间歇性低氧的动物模型中每天造模8h,持续4周,RH组的大鼠在常规下饲养3周,在建模结束时抽取大鼠动脉血立即行血气分析。空腹12h后静脉取血离心取上清液后用过氧化物酶法检测血清中血糖及放射免疫法检测大鼠血清胰岛素,ELISA法检测血清瘦素(leptin)和游离脂肪酸(FFA)。取出大鼠肾脏组织,q PCR法检测大鼠肾脏GLUT-2、IRS-2的m RNA表达,Western blotting法检测GLUT-2、IRS-2蛋白表达;免疫组化法检测大鼠肾脏GLUT-2、IRS-2蛋白表达。结果:1.control组大鼠血氧饱和度≥95%,CIH组的血氧饱和度≤85%,RH组血氧饱和度≥86%;2.CIH组大鼠空腹血糖、血清胰岛素、胰岛素抵抗指数较control组、RH组明显升高(P0.05);RH组高于control组(P0.05);3.Leptin、FFA在CIH的浓度高于control组和RH组,(P0.05);RH组高于control组,(P0.05);4.GLUT-2、IRS-2的m RNA表达在CIH组高于control组和RH组,(P0.05);RH组高于control组,(P0.05);5.CIH组的GLUT-2、IRS-2的蛋白表达较control组和RH组升高(P0.05);RH组高于control组(P0.05)结论:慢性间歇性低氧升高大鼠空腹血糖、胰岛素、leptin及FFA,上调大鼠肾脏GLUT-2、IRS-2的表达,增强胰岛素抵抗,降低胰岛素敏感性。
[Abstract]:Objective: Sleep-disordered breathing disorder (SDBs) has been found to be closely related to various systemic diseases in recent years. The most common clinical manifestation of obstructive sleep apnea hypopnea syndrome (OSAHS) is frequent restlessness or apnea during sleep. Repeated intermittent hypoxia in sleep causes damage to multiple systems and organs throughout the body. According to the pathophysiological characteristics of OSAHS, a chronic intermittent hypoxic experimental animal model was established, which provides a reliable experimental platform for the study of sleep respiratory diseases. By establishing chronic intermittent hypoxia and reoxygenation animal models, the effects of chronic intermittent hypoxia on lipid factors and the effects of reoxygenation on glucose metabolism and the expression of glucose-transporter 2- GLUT-2and insulin receptor substrate 2- IRS-2 in rats were studied. Methods: Twenty-four adult Sprague-Dawley male rats were randomly divided into control group, chronic intermittent hypoxia group, reoxygenation group and RH group. At the end of modeling, arterial blood was extracted from rats for blood gas analysis. Serum glucose was detected by peroxidase method and serum leptin was detected by radioimmunoassay (RIA) and serum leptin (leptin) and free fatty acid (FFAA) were detected by radioimmunoassay (RIA). The expression of GLUT-2IRS-2 in rat kidney was detected by Q PCR method, and the expression of GLUT-2mIRS-2 protein was detected by Western blotting, and the expression of GLUT-2mIRS-2 protein was detected by immunohistochemistry. Results 1. The blood oxygen saturation of rats in the control group 鈮，

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