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慢性間歇性低氧對大鼠腎臟葡萄糖轉(zhuǎn)運(yùn)蛋白2及胰島素受體底物2表達(dá)的影響

發(fā)布時(shí)間:2018-06-04 11:28

  本文選題:慢性間歇性低氧 + 胰島素抵抗。 參考:《重慶醫(yī)科大學(xué)》2017年碩士論文


【摘要】:目的:睡眠呼吸疾病(Sleep-disordered breathing,SDB)在近幾年的研究中發(fā)現(xiàn)與全身各種疾病有著密切關(guān)系。在臨床上最為常見的是阻塞性睡眠呼吸暫停低通氣綜合征(Obstructive sleep apnea hypopnea syndrome,OSAHS)表現(xiàn)為在睡眠狀態(tài)下出現(xiàn)的頻繁的呼吸不暢或者呼吸暫停,機(jī)體在睡眠中反復(fù)出現(xiàn)間歇性缺氧導(dǎo)致全身多個(gè)系統(tǒng)、多個(gè)器官的損害。根據(jù)OSAHS的病理生理特征建立一個(gè)符合其特征的慢性間歇性低氧實(shí)驗(yàn)動物模型,為研究睡眠呼吸疾病提供一個(gè)可靠的實(shí)驗(yàn)平臺。通過建立慢性間歇性低氧及復(fù)氧的動物模型,探討慢性間歇性低氧所致的脂肪因子以及復(fù)氧對大鼠糖代謝及腎臟葡萄糖轉(zhuǎn)運(yùn)蛋白2(GLUT-2)、胰島素受體底物2(IRS-2)表達(dá)的影響。方法:將24只SD雄性成年大鼠隨機(jī)分為對照組(control),慢性間歇性低氧組(CIH),復(fù)氧組(RH)。CIH組和RH組在慢性間歇性低氧的動物模型中每天造模8h,持續(xù)4周,RH組的大鼠在常規(guī)下飼養(yǎng)3周,在建模結(jié)束時(shí)抽取大鼠動脈血立即行血?dú)夥治。空?2h后靜脈取血離心取上清液后用過氧化物酶法檢測血清中血糖及放射免疫法檢測大鼠血清胰島素,ELISA法檢測血清瘦素(leptin)和游離脂肪酸(FFA)。取出大鼠腎臟組織,q PCR法檢測大鼠腎臟GLUT-2、IRS-2的m RNA表達(dá),Western blotting法檢測GLUT-2、IRS-2蛋白表達(dá);免疫組化法檢測大鼠腎臟GLUT-2、IRS-2蛋白表達(dá)。結(jié)果:1.control組大鼠血氧飽和度≥95%,CIH組的血氧飽和度≤85%,RH組血氧飽和度≥86%;2.CIH組大鼠空腹血糖、血清胰島素、胰島素抵抗指數(shù)較control組、RH組明顯升高(P0.05);RH組高于control組(P0.05);3.Leptin、FFA在CIH的濃度高于control組和RH組,(P0.05);RH組高于control組,(P0.05);4.GLUT-2、IRS-2的m RNA表達(dá)在CIH組高于control組和RH組,(P0.05);RH組高于control組,(P0.05);5.CIH組的GLUT-2、IRS-2的蛋白表達(dá)較control組和RH組升高(P0.05);RH組高于control組(P0.05)結(jié)論:慢性間歇性低氧升高大鼠空腹血糖、胰島素、leptin及FFA,上調(diào)大鼠腎臟GLUT-2、IRS-2的表達(dá),增強(qiáng)胰島素抵抗,降低胰島素敏感性。
[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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