慢性间歇低氧和复氧对非肥胖型大鼠糖代谢的影响
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摘要
第一部分：慢性间歇低氧及复氧对非肥胖型大鼠糖耐量和胰岛素抵抗程度的影响
目的探讨慢性间歇低氧(CIH)5周及低氧后复氧3周、6周对非肥胖型大鼠糖耐量和胰岛素抵抗程度的影响。
方法将大鼠暴露于间歇低氧环境35天后(PO27-21%),空腹状态下经尾静脉取血离心,用酶联免疫吸附法(ELISA)检测血清中胰岛素水平,通过计算稳态模型评估胰岛素抵抗指数(HOMA-IR)观察大鼠是否出现胰岛素抵抗；并行腹腔注射葡萄糖耐量试验(IPGTT),即空腹状态下经腹腔注射葡萄糖(2g/kg),在0、30、60、120min监测大鼠血糖,通过计算血糖曲线下面积(AUCG)观察大鼠是否出现糖耐量异常。
结果间歇低氧组大鼠较对照组大鼠糖耐量明显降低(AUCG 17.9±0.7 VS 21.8±1.1 P<0.01)、胰岛素抵抗指数明显增加(HOMA-IR 0.53±0.96 VS 1.16±0.23)(P<0.01),经过慢性间歇3周、6周持续复氧处理,糖耐量和胰岛素抵抗均显著改善(P<0.05),但持续复氧3周和持续复氧6周组对比糖耐量和胰岛素抵抗程度均无差异。
结论慢性间歇低氧5周可导致大鼠糖耐量降低,出现胰岛素抵抗,而间歇低氧后3周、6周持续复氧均可以纠正这种状况。
第二部分：慢性间歇低氧对非肥胖型大鼠脂肪组织低氧状况和脂肪因子分泌的影响
目的：研究慢性间歇低氧(CIH)5周对非肥胖型大鼠脂肪组织低氧状况、血清脂肪因子瘦素、脂联素和抵抗素水平的影响。
方法：将大鼠随机分为两组：对照组(Control)和慢性间歇低氧组(CIH),在对CIH组进行5周间歇低氧后,分别采用Real-time PCR和Western-blot方法检测各组大鼠脂肪组织中缺氧诱导因子1α(HIF-1α)基因和蛋白的表达水平,应用酶联免疫吸附试验(ELISA)检测大鼠血清中脂肪因子脂联素、抵抗素和瘦素的水平。
结果：慢性间歇低氧5周后,CIH组大鼠脂肪组织HIF-1α基因和蛋白表达较对照组明显增加,其相对表达量均有统计学意义,说明慢性间歇低氧导致大鼠出现脂肪组织低氧(ATH)。CIH组大鼠血清瘦素和抵抗素水平较对照组明显增高(P<0.05),血清脂联素水平显著下降(P<0.05)。
结论：慢性间歇低氧导致非肥胖大鼠出现脂肪组织低氧(ATH)；慢性间歇低氧引起大鼠脂肪因子分泌紊乱,表现为脂联素水平下降、瘦素和脂联素水平升高。
Part I:Chronic intermittent hypoxia and reoxygenation affect glucose tolerance and insulin resistance in non-obese rats
[Objective] To explore the effects of chronic intermittent hypoxia and reoxygenation on glucose tolerance and insulin resistance in non-obese rats.
[Methods] Sprague-Dawley rats were exposed to intermittent hypoxia environment(PO27-21%) for five weeks, then fasting serum insulin was detected using enzyme linked immunosorbent assay(ELISA), and intraperitoneal glucose tolerance test (IPGTT) was carried out (2g/kg) to evaluate the effects of intermittent hypoxia on glucose tolerance of rats.
[Results] Long term intermittent hypoxia significantly decrease the glucose tolerance in rats (17.9±0.7 VS 21.8±1.1 P<0.01), increase insulin resistance index (0.53±0.96 VS 1.16±0.23) (P<0.01), and the impaired glucose tolerance and insulin resistance were improved after a period of reoxygenation(3 weeks or 6 weeks), however,6 weeks of reoxygenation didn't get better results compared with the shorter term reoxygenation
[Conclusions] Chronic intermittent hypoxia leads to impaired glucose tolerance and insulin resistance in non-obese rats, and reoxygenation can correct such disorders.
Part II:Effect of chronic intermittent hypoxia on adipose tissue hypoxia and adiokines
[Objective] Recent studies indicate that Adipose Tissue Hypoxia(ATH) plays a great role in the endocrinal disorders associated with obese, the aim of this study was to explore whether systemic intermittent hypoxia can lead to ATH in otherwise non-obese rats, also the effects of chronic intermittent hypoxia on serum adipokines such as leptin、adiponectin and resistin.
[Methods] Sprague-Dawley rats were divided into two groups:Control group and chronic intermittent hypoxia (CIH) group. After exposure to intermittent hypoxia for 5 weeks, Hypoxia inducible factor-1α(HIF-1α) gene and protein in adipose tissue, which will be increased in adipose tissue hypoxia, were detected with real-time PCR and western blot method, serum leptin、adiponectin and resistin were measured using enzyme linked immunosorbent assay(ELISA).
[Results] HIF-1αm RNA and HIF-1αprotein were significantly increased in CIH group after exposure to intermittent hypoxia for 5 weeks; serum leptin and resistin were elevated in CIH group (P<0.05), adiponectin was decreased dramatically (24.04±8.48 VS 17.09±4.92, P<0.05).
[Conclusion] Chronic intermittent hypoxia leads to adipose tissue hypoxia in non-obese rats; CIH also cause endocrine disorder in adipose tissue with an increase in leptin and resistin and decrease in adiponectin.
目的探讨慢性间歇低氧(CIH)5周及低氧后复氧3周、6周对非肥胖型大鼠糖耐量和胰岛素抵抗程度的影响。
方法将大鼠暴露于间歇低氧环境35天后(PO27-21%),空腹状态下经尾静脉取血离心,用酶联免疫吸附法(ELISA)检测血清中胰岛素水平,通过计算稳态模型评估胰岛素抵抗指数(HOMA-IR)观察大鼠是否出现胰岛素抵抗；并行腹腔注射葡萄糖耐量试验(IPGTT),即空腹状态下经腹腔注射葡萄糖(2g/kg),在0、30、60、120min监测大鼠血糖,通过计算血糖曲线下面积(AUCG)观察大鼠是否出现糖耐量异常。
结果间歇低氧组大鼠较对照组大鼠糖耐量明显降低(AUCG 17.9±0.7 VS 21.8±1.1 P<0.01)、胰岛素抵抗指数明显增加(HOMA-IR 0.53±0.96 VS 1.16±0.23)(P<0.01),经过慢性间歇3周、6周持续复氧处理,糖耐量和胰岛素抵抗均显著改善(P<0.05),但持续复氧3周和持续复氧6周组对比糖耐量和胰岛素抵抗程度均无差异。
结论慢性间歇低氧5周可导致大鼠糖耐量降低,出现胰岛素抵抗,而间歇低氧后3周、6周持续复氧均可以纠正这种状况。
第二部分：慢性间歇低氧对非肥胖型大鼠脂肪组织低氧状况和脂肪因子分泌的影响
目的：研究慢性间歇低氧(CIH)5周对非肥胖型大鼠脂肪组织低氧状况、血清脂肪因子瘦素、脂联素和抵抗素水平的影响。
方法：将大鼠随机分为两组：对照组(Control)和慢性间歇低氧组(CIH),在对CIH组进行5周间歇低氧后,分别采用Real-time PCR和Western-blot方法检测各组大鼠脂肪组织中缺氧诱导因子1α(HIF-1α)基因和蛋白的表达水平,应用酶联免疫吸附试验(ELISA)检测大鼠血清中脂肪因子脂联素、抵抗素和瘦素的水平。
结果：慢性间歇低氧5周后,CIH组大鼠脂肪组织HIF-1α基因和蛋白表达较对照组明显增加,其相对表达量均有统计学意义,说明慢性间歇低氧导致大鼠出现脂肪组织低氧(ATH)。CIH组大鼠血清瘦素和抵抗素水平较对照组明显增高(P<0.05),血清脂联素水平显著下降(P<0.05)。
结论：慢性间歇低氧导致非肥胖大鼠出现脂肪组织低氧(ATH)；慢性间歇低氧引起大鼠脂肪因子分泌紊乱,表现为脂联素水平下降、瘦素和脂联素水平升高。
Part I:Chronic intermittent hypoxia and reoxygenation affect glucose tolerance and insulin resistance in non-obese rats
[Objective] To explore the effects of chronic intermittent hypoxia and reoxygenation on glucose tolerance and insulin resistance in non-obese rats.
[Methods] Sprague-Dawley rats were exposed to intermittent hypoxia environment(PO27-21%) for five weeks, then fasting serum insulin was detected using enzyme linked immunosorbent assay(ELISA), and intraperitoneal glucose tolerance test (IPGTT) was carried out (2g/kg) to evaluate the effects of intermittent hypoxia on glucose tolerance of rats.
[Results] Long term intermittent hypoxia significantly decrease the glucose tolerance in rats (17.9±0.7 VS 21.8±1.1 P<0.01), increase insulin resistance index (0.53±0.96 VS 1.16±0.23) (P<0.01), and the impaired glucose tolerance and insulin resistance were improved after a period of reoxygenation(3 weeks or 6 weeks), however,6 weeks of reoxygenation didn't get better results compared with the shorter term reoxygenation
[Conclusions] Chronic intermittent hypoxia leads to impaired glucose tolerance and insulin resistance in non-obese rats, and reoxygenation can correct such disorders.
Part II:Effect of chronic intermittent hypoxia on adipose tissue hypoxia and adiokines
[Objective] Recent studies indicate that Adipose Tissue Hypoxia(ATH) plays a great role in the endocrinal disorders associated with obese, the aim of this study was to explore whether systemic intermittent hypoxia can lead to ATH in otherwise non-obese rats, also the effects of chronic intermittent hypoxia on serum adipokines such as leptin、adiponectin and resistin.
[Methods] Sprague-Dawley rats were divided into two groups:Control group and chronic intermittent hypoxia (CIH) group. After exposure to intermittent hypoxia for 5 weeks, Hypoxia inducible factor-1α(HIF-1α) gene and protein in adipose tissue, which will be increased in adipose tissue hypoxia, were detected with real-time PCR and western blot method, serum leptin、adiponectin and resistin were measured using enzyme linked immunosorbent assay(ELISA).
[Results] HIF-1αm RNA and HIF-1αprotein were significantly increased in CIH group after exposure to intermittent hypoxia for 5 weeks; serum leptin and resistin were elevated in CIH group (P<0.05), adiponectin was decreased dramatically (24.04±8.48 VS 17.09±4.92, P<0.05).
[Conclusion] Chronic intermittent hypoxia leads to adipose tissue hypoxia in non-obese rats; CIH also cause endocrine disorder in adipose tissue with an increase in leptin and resistin and decrease in adiponectin.
引文
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[2]上海市医学会呼吸病学分会睡眠呼吸疾病学组.上海市30岁以上人群睡眠呼吸暂停低通气综合征流行病学调查,中华结核和呼吸杂志,2003,26：268-272.
[3]Friedman M, Schalch P, Lin HC. Palatal implants for the treatment of snoring and obstructive sleep apnea/hypopnea syndrome. Otolaryngol Head Neck Surg.2008,138:209-216.
[4]Cross MD, Vennelle M, Engleman HM. Comparison of CPAP titration at home or the sleep laboratory in the sleep apnea hypopnea syndrome. Sleep. 2006,29:1451-1455.
[5]Friedman M, Ibrahim H, Lowenthal S. Uvulopalatoplasty (UP2):A modified technique for selected patients. Laryngoscope.2004,114 (3): 441-449.
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[7]Engleman HM, Douglas NJ. Sleep center dot 4:Sleepiness, cognitive function, and quality of life in obstructive sleep apnoea/hypopnoea syndrome. Thorax,2004,59(7):618-622.
[8]Fornas C, Ballester E, Arteta E, et al. Measurement of general health status in obstructive sleep apnea hypopnea patients. Sleep,1995, 18(10):876-879.
[9]Hoy CJ, Vennelle M, Kingshott RN, et al. Can intensive support improve continuous positive airway pressure use in patients with the sleep apnea/hypopnea syndrome? Am J Respir Crit Care Med,1999, 159(4): 1096-1100.
[10]Meslier N, Lebrun T, Grillier-Lanoir V, et al. A French survey of 3,225 patients treated with CPAP for obstructive sleep apnoea: benefits, tolerance, compliance and quality of life. Eur Respir J, 1998,12(1):185-192.
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