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.
引文
[1]Young T, Paha M, Dempsey j, et al. The occurance of sleep-disordered breathingamong middle-aged adults. New Engl J Med,1993,328:1230-1235.
[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症流行病学调查.中华结核与呼吸杂志,2003,26:268-272.
[3]Mihaere KM, Harris R, Gander PH, et al. Obstructive sleep apnea in New Zealand adults:prevalence and risk factors among Maori and non-Maori. Sleep,2009,32(7):949-56.
[4]Reddy EV, Kadhiravan T, Mishra HK, et al. Prevalence and risk factors of obstructive sleep apnea among middle-aged urban Indians:a community-based study. Sleep Med,2009,10(8):913-8.
[5]Robinso GV, Stradling JR, Davies RO. Obstructive sleep apnoea/hypopnoea syndrome and hypertension. Thorax.2004, 59(12):1089-1094.
[6]Hamilton GS, Solin P, Naughton MT. Obstructive sleep apnoea and cardiovascular disease. Int Med J,2004,34(7):420-426.
[7]Meslier N, Gagnadoux F, Giraud P et al. Impaired glucose-insulin metabolism in males with obstructive sleep apnoea syndrome. Eur Respir J,2003,22:156-160.
[8]West SD, Nicoll DJ, Stradling JR. Prevalence of obstructive sleep apnoea in men with type 2 diabetes. Thorax,2006,61:945-950.
[9]Punjabi NM, Ahmed MM, Polotsky VY, et al. Sleep-disordered breathing, glucose intolerance, and insulin resistance. Respir Physiol Neurobiol, 2003,136(2-3):167-178.
[10]Aronsohn RS, Whitmore H, Van Cauter E, et al. Impact of Untreated Obstructive Sleep Apnea on Glucose Control in Type 2 Diabetes. Am J Respir Crit Care Med,2010,181(5):507-513.
[11]Vgontzas AN, Bixler EO, Chrousos GP. Sleep apnea is a manifestation of the metabolic syndrome. Sleep Med Rev,2005,9:211-24.
[12]Meslier N, Gagnadoux F, Giraud P, et al. Impaired glucose-insulin metabolism in males with obstructive sleep apnoea syndrome. Eur Respir J,2003,22:156-60.
[13]AN Vgontzas, DA Papanicolaou, EO Bixler, et al. Sleep apnea and daytime sleepiness and fatigue:relation to visceral obesity, insulin resistance, and hypercytokinemia. J Clin Endocrinol Metab, 2000,85:1151-1158.
[14]Botros N, Concato J, Mohsenin V, et al. Obstructive Sleep Apnea as a Risk Factor for Type 2 Diabetes. Am J Med,2009,122(12):1122-1127.
[15]Polotsky VY, Patil SP, Savransky V, et al. Obstructive Sleep Apnea, Insulin Resistance, and Steatohepatitis in Severe Obesity. Am J Respir Crit Care Med,2009,179(3):228-234.
[16]Ip MSM, Lam B, Ng MMT, et al. Obstructive sleep apnea is independently associated with insulin resistance. Am J Respir Crit Care Med,2002,165(5):670-676.
[17]Muraki I, Tanigawa T, Yamagishi K, et al. Nocturnal intermittent hypoxia and the development of type 2 diabetes:the Circulatory Risk in Communities Study (CIRCS). Diabetologia,2010,53(3):481-488.
[18]Cuhadaroglu C, Utkusava$ A, Ozturk L, et al. Effects of nasal CPAP treatment on insulin resistance, lipid profile, and plasma leptin in sleep apnea. Lung.2009,187(2):75-81.
[19]Dawson A, Abel SL, Loving RT, et al. CPAP therapy of obstructive sleep apnea in type 2 diabetics improves glycemic control during sleep. J Clin Sleep Med,2008,4(6):538-42.
[20]Schahin SP, Nechanitzky T, Dittel C, et al. Long-term improvement of insulin sensitivity during CPAP therapy in the obstructive sleep apnoea syndrome.Med Sci Monit,2008,14(3):CR117-21.
[21]Ye J, Gao Z, Yin J, He H. Hypoxia is a potential risk factor for chronic inflammation and adiponectin reduction in adipose tissue of ob/ob and dietary obese mice. Am J Physiol Endocrinol Metab,2007,293: E1118-E1128.
[22]Bolinder J, Kerckhoffs DA, Moberg E, et al. Rates of skeletal muscle and adipose tissue glycerol release in nonobese and obese subjects. Diabetes,2000,49:797-802.
[23]Kampf C, Bodin B, Kallskog O, et al. Marked increase in white adipose tissue blood perfusion in the type 2 diabetic GK rat. Diabetes, 2005,54:2620-2627.
[24]Ye J, Gao Z, Yin J, He H. Hypoxia is a potential risk factor for chronic inflammation and adiponectin reduction in adipose tissue of ob/ob and dietary obese mice. Am J Physiol Endocrinol Metab,2007,293:E1118-E1128.
[25]Hosogai N, Fukuhara A, Oshima K, Miyata Y, Tanaka S, Segawa K, et al. Adipose tissue hypoxia in obesity and its impact on adipocytokine dysregulation. Diabetes,2007,56:901-911.
[26]Hotamisligil GS. Inflammation and metabolic disorders. Nature,2006,444:860-867.
[27]Ailhaud G. Adipose tissue as a secretory organ:from adipogenesis to the metabolic syndrome. C R Biol,2006,329(8):570-577.
[28]Han SH, Sakuma I, Shin EK, et al. Antiatherosclerotic and Anti-Insulin Resistance Effects of Adiponectin:Basic and Clinical Studies. Prog Cardiovasc Dis,2009,52(2):126-140.
[29]Braun B, Rock PB, Zamudio S, et al. Women at altitude:short-term exposure to hypoxia and or alpha(1)-adrenergic blockade reduces insulin sensitivity. J Appl Physiol,2001,91:623-631.
[30]Larsen JJ, Hansen JM, Olsen NV, et al. The effect of altitude hypoxia on glucose homeostasis in men. J Physiol,1997,504:241-249.
[31]Yokoe T, Alonso LC, Romano LC, et al. Intermittent hypoxia reverses the diurnal glucose rhythm and causes pancreaticβ-cell replication in mice. J Physiol,2008,586(3):899—911.
[32]Polotsky VY, Li J, Punjabi NM, et al. Intermittent hypoxia increases insulin resistance in genetically obese mice. J Physiol,2003,552 Pt 1:253-264.
[33]Sulit L, Storfer-Isser A, Kirchner HL, et al. Differences in polysomnography predictors for hypertension and impaired glucose tolerance. Sleep,2006,29:777-783.
[34]Reichmuth KJ, Austin D, Skatrud JB, et al. Association of sleep apnea and type Ⅱ diabetes-A population-based study. Am J Respir Crit Care Med,,2005,172(12):1590-1595.
[35]Botros N, Concato J, Mohsenin V, et al. Obstructive Sleep Apnea as a Risk Factor for Type 2 Diabetes. Am J Med,2009,122(12):1122-1127.
[36]Oltmanns KM, Gehring H, Rudolf S, et al. Hypoxia causes glucose intolerance in humans. Am J Respir Crit Care Med,2004,169:1231-1237.
[37]Louis M, Punjabi NM. Effects of acute intermittent hypoxia on glucose metabolism in awake healthy volunteers. J Appl Physiol,2009,106(5):1538-1544.
[38]Iiyori N, Alonso LC, et al. Intermittent hypoxia causes insulin resistance in lean mice independent of autonomic activity. Am J Respir Crit Care Med,2007,175(8):851-857.
[39]Savransky V, Nanayakkara A, Vivero A, et al. Chronic intermittent hypoxia predisposes to liver injury. Hepatology,2007,45 (4):1007-1013.
[40]Chen L, Cao ZL, Han F, et al. Chronic intermittent hypoxia from pedo-stage decreases glucose transporter 4 expression in adipose tissue and causes insulin resistance. Chin Med J, 2010,123(4):463-470.
[41]Aouad LJ, Tam K, Waters KA. Effects of acute intermittent hypercapnic hypoxia on insulin sensitivity in piglets using euglycemic clamp. Metabolism,2008,57(8):1056-1063.
[42]Brazil DP, Hemmings BA. Ten years of protein kinase B signalling: a hard Akt to follow. Trends Biochem Sci,2001,26:657-664.
[43]Pirola L, Johnston AM, Van Obberghen E. Modulation of insulin action. Diabetologia,2004,47:170-184.
[44]Bevan P. Insulin signalling. J Cell Sci,2001,114:1429-1430.
[45]Wellen KE, Hotamisligil GS. Inflammation, stress, and diabetes. J Clin Invest,2005,115,1111-1119.
[46]Hotamisligil GS. Inflammation and metabolic disorders. Nature,2006,444:860-867.
[47]Sartipy P, Loskutoff DJ. Monocyte chemo-attractant protein 1 in obesity and insulin resistance. Proc Natl Acad Sci,2003,100:7265-7270.
[48]Ye J, Gao Z, Yin J, He H. Hypoxia is a potential risk factor for chronic inflammation and adiponectin reduction in adipose tissue of ob/ob and dietary obese mice. Am J Physiol Endocrinol, Metab,2007,293:E1118-E1128.
[49]Hosogai N, Fukuhara A, Oshima K, Miyata Y, Tanaka S, Segawa K, et al. Adipose tissue hypoxia in obesity and its impact on adipocytokine dysregulation. Diabetes,2007,56:901-911.
[50]Levy P, Bonsignore MR, Eckel J. Sleep, sleep-disordered breathing and metabolic consequences.Eur Respir J,2009,34(1):243-260.
[51]Cuhadaroglu C, Utkusavas A, Ozturk L, et al. Effects of Nasal CPAP Treatment on Insulin Resistance, Lipid Profile, and Plasma Leptin in Sleep Apnea. Lung,2009,187(2):75-81.
[52]Yamamoto Y, Fujiuchi S, Hiramatsu M, et al. Resistin Is Closely Related to Systemic Inflammation in Obstructive Sleep Apnea. Respiration,2008,76(4):377-385.
[53]Grosfeld A, Zilberfarb V, Turban S, et al. Hypoxia increases leptin expression in human PAZ6 adipose cells. Diabetologia,2002,45:527-30.
[54]Meissner U, Ostreicher I, Allabauer I, et al. Synergistic effects of hypoxia and insulin are regulated by different transcriptional elements of the human leptin promoter. Biochem Biophys Res Commun, 2003,303:707-12.
[55]Rausch ME, Weisberg S, Vardhana P, et al. Obesity in C57BL/6J mice is characterized by adipose tissue hypoxia and cytotoxic T-cell infiltration. Int J Obes,2008,32:451-463.
[56]Hosogai N, Fukuhara A, Oshima K, et al. Adipose tissue hypoxia in obesity and its impact on adipocytokine dysregulation. Diabetes,2007, 56:901-911.
[57]Semenza G. Signal transduction to hypoxia-inducible factor 1. Biochem Pharmacol,2002,64:993-998.
[58]Hosogai N, Fukuhara A, Oshima K, et al. Adipose tissue hypoxia in obesity and its impact on adipocytokine dysregulation. Diabetes, 2007,56:901-911.
[59]Rausch ME, Weisberg S, Vardhana P, et al. Obesity in C57BL/6J mice is characterized by adipose tissue hypoxia and cytotoxic T-cell infiltration. Int J Obes,2008,32:451-463.
[60]Tilg H, Moschen AR. Adipocytokines:mediators linking adipose tissue, inflammation and immunity. Nat Rev Immunol,2006,6:772-783.
[61]Ailhaud G. Adipose tissue as a secretory organ:from adipogenesis to the metabolic syndrome. C R Biol,2006,329(8):570-577.
[62]Wang B, Wood IS, Trayhurn P. Dysregulation of the expression and secretion of inflammation-related adipokines by hypoxia in human adipocytes. Pflugers Arch,2007,455(3):479-92.
[63]E Hu, et al. AdipoQ is a novel adipose-specific gene dysregulated in obesity. J Biol Chem,1996,271:10697-10703.
[64]K Hotta et al. Circulating concentrations of the adipocyte protein adiponectin are decreased in parallel with reduced insulin sensitivity during the progression to type 2 diabetes in rhesus monkeys. Diabetes,2001,50:1126-1133.
[65]Raff H, Bruder ED, Jankowski BM, et al. Effect of neonatal hypoxia on leptin, insulin, growth hormone and body composition in the rat. Horm Metab Res,2001,33:151-5.
[66]Chaiban JT, Bitar FF, Azar ST. Effect of chronic hypoxia on leptin, insulin, adiponectin, and ghrelin. Metabolism,2008,57(8):1019-1022.
[67]Y. Arita et al. Paradoxical decrease of an adipose-specific protein, adiponectin, in obesity. Biochem Biophys Res Commun,1999,257:79-83.
[68]K. Hotta et al. Plasma concentrations of a novel, adipose-specific protein, adiponectin, in type 2 diabetic patients. Arterioscler Thromb Vasc Biol,2000,20:1595-1599.
[69]Makino S, Handa H, Suzukawa K, et al. Sugimoto T:Obstructive sleep apnoea syndrome, plasma adiponectin levels and insulin resistance. Clin Endocrinol,2006,64:12-19.
[70]Zhang XL, Yin KS, Mao H, et al. Serum adiponectin level in patients with obstructive sleep apnea hypopnea syndrome. Chin Med J, 2004,117:1603-1606.
[71]Masserini B, Morpurgo PS, Donadio F, et al. Reduced levels of adiponectin in sleep apnea syndrome. J Endocrinol Invest, 2006,29:700-705.
[72]de Lima AM, Franco CM, de Castro CM, et al. Effects of Nasal Continuous Positive Airway Pressure Treatment on Oxidative Stress and Adiponectin Levels in Obese Patients with Obstructive Sleep Apnea. Respiration,2010,79(5):370-376.
[73]Wolk R, Svatikova A, Nelson CA, et al. Plasma levels of adiponectin, a novel adipocyte-derived hormone, in sleep apnea. Obes Res,2005, 12:186-190.
[74]Fasshauer M, Klein J, Neumann S, et al. Hormonal regulation of adiponectin gene expression in 3T3-L1 adipocytes. Biochem Biophys Res Commun,2002,290:1084-1089.
[75]Semenza GL, Agani F, Feldser D, et al. Hypoxia, HIF-1, and the pathophysiology of common human diseases. Adv Exp Med Biol,2000,475: 123-130.
[76]Ziemke F, Mantzoros CS. Adiponectin in insulin resistance:lessons from translational research. Am J Clin Nutr,2010,91(1):258S-261S.
[77]T Kadowaki, K Hara, T Yamauchi, et al. Molecular mechanism of insulin resistance and obesity, Exp Biol Med,2003,228:1111-1117.
[78]AH Berg, TP Combs, X Du, et al. The adipocyte-secreted protein Acrp30 enhances hepatic insulin action, Nat Med,2001,7:947-953.
[79]Mercedes Gil-Campos, Ramon Canete, Angel Gil. Adiponectin, the missing link in insulin resistance and obesity. Clin Nutr, 2004,23 (5):963-974.
[80]Ahima RS, Flier JS. Leptin. Annu Rev Physiol,2000,62:413-437
[81]Meissner U, Spranger R, Lehner M, et al. Hypoxia-induced leptin production in human trophoblasts does not protect from apoptosis. Eur J Endocrinol,2005,153:455-461.
[82]Tokuda F, Sando Y, Matsui H, et al. Serum Levels of Adipocytokines, Adiponectin and Leptin, in Patients with Obstructive Sleep Apnea Syndrome. Intern Med,2008,47(21):1843-1849.
[83]Cuhadaroglu C, Utkusavas A, Ozturk L, et al. Effects of Nasal CPAP Treatment on Insulin Resistance, Lipid Profile, and Plasma Leptin in Sleep Apnea. Lung,2009,187(2):75-81.
[84]Kapsimalis F, Varouchakis G, Manousaki A, et al. Association of sleep apnea severity and obesity with insulin resistance, C-reactive protein, and leptin levels in male patients with obstructive sleep apnea. Lung,186(4):209-217.
[85]Shin Eyun-Jung, Schram Kristin, Zheng Xi-Long, et al. Leptin attenuates hypoxia/reoxygenation-induced activation of the intrinsic pathway of apoptosis in rat H9c2 cells. J Cell Physiol, 2009,221 (2):490-7.
[86]Sherry CL, Kramer JM, York JM, et al. Behavioral recovery from acute hypoxia is reliant on leptin. Brain Behav Immun,2009,23(2):169-175.
[87]Muzumdar R, Ma X, Yang X, et al. Physiologic effect of leptin on insulin secretion is mediated mainly through central mechanism. FASEB J,2003,17:1130-1132.
[88]Park S, Hong SM, Sung SR, et al. Long-term effects of central leptin and resistin on body weight, insulin resistance, and beta-cell function and mass by the modulation of hypothalamic leptin and insulin signaling. Endocrinology,2008,149(2):445-454.
[89]Ahima RS, Flier JS. Leptin. Annu Rev Physiol,2000,62:413-437.
[90]Myers MG, Cowley MA, Munzberg H. Mechanisms of leptin action and leptin resistance. Annu Rev Physiol,2008,70:537-556.
[91]Kim KH, Zhao, Moon Yangsoo, et al. Dominant inhibitory adipocyte-specific secretory factor (ADSF)/resistin enhances adipogenesis and improves insulin sensitivity. Proc Natl Acad Sci,2004,101:6780-6785
[92]CC Zou, L Liang, F Hong, et al. Serum adiponectin, resistin levels and non alcoholic fatty liver disease in obese children, Endocrine J,2005,52:519-524.
[93]de Luis DA, Sagrado MG, Conde R, et al. Relation of resistin levels with cardiovascular risk factors and insulin resistance in non-diabetes obese patients. Diabetes Res Clin Pract, 2009,84 (2):174-178.
[94]Yamamoto Y, Fujiuchi S, Hiramatsu M, et al. Resistin Is Closely Related to Systemic Inflammation in Obstructive Sleep Apnea. Respiration,2008,76(4):377-385.
[1]Young T, Paha M, Dempsey j, et al. The occurance of sleep-disordered breathingamong middle-aged adults. New Engl J Med.1993,328:1230-1235.
[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.
[6]Gulbay BE, Acican T, Onen ZP. Health-related quality of life in patients with sleep-related breathing disorders:Relationship with nocturnal parameters, daytime symptoms and comorbid diseases. Respiration,2008,75(4):393-401.
[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.
[11]Jing JY, Huang TC, Cui W, et al. Effect on quality of life of continuous positive airway pressure in patients with obstructive sleep apnea syndrome:A meta-analysis. Lung,2008,186(3):131-144.
[12]Kribbs NB, Pack AI, Kline LR, et al. Effects of one night without nasal CPAP treatment on sleep and sleepiness in patients with obstructive sleep apnea. Am Rev Respir Dis,1993,147(5):1162-1168.
[13]Izci B, Ardic S, Firat H, et al. Reliability and validity studies of the Turkish version of the Epworth Sleepiness Scale. Sleep Breath, 2008,12(2):161-168.
[14]Rosenthal LD, Dolan DC. The Epworth sleepiness scale in the identification of obstructive sleep apnea. J Nerv Ment Dis, 2008,196(5):429-431.
[15]Cross MD, Vennelle M, Engleman HM, et al. Comparison of CPAP titration at home or the sleep laboratory in the sleep apnea hypopnea syndrome. Sleep,2006,29:1451-1455.
[16]de Mello-Filho, Francisco Verissimo, Faria Ana Celia, et al. Maxillo mandibular advancement surgery for the treatment of obstructive sleep apnea/hypopnea syndrome (OSAHS). Medicina (Ribeirao Preto).2006;39(2):227-234.
[17]Smith S, Sullivan KA. A reliable change index (RCI) for the Epworth sleepiness scale (ESS). Sleep Med,2007,9:102-102.
[18]Inoue M, Kasai T, Kawana F, Narui K. Response shift of subjective sleepiness in patients with obstructive sleep apnea-hypopnea syndrome. Sleep Biol Rhyth,2007,5(2):95-99.
[19]Kawahara S, Akashiba T, Akahoshi T, et al. Nasal CPAP improves the quality of life and lessens the depressive symptoms in patients with obstructive sleep apnea syndrome. Intern Med,2005,44:422-7.
[20]Nguyen Anh Tu Duy, Baltzan Marc A, Small David, et al. Clinical reproducibility of the Epworth Sleepiness Scale. J Clin Sleep Med, 2006,2 (2):170-4.
[21]Weaver, TE; Laizner, AM; Evans, LK, et al. An instrument to measure functional status outcomes for disorders of excessive sleepiness. SLEEP,1997,20(10):835-843.
[22]Massie CA, Hart RW. Clinical outcomes related to interface type in patients with obstructive sleep apnea/hypopnea syndrome who are using continuous positive airway pressure. Chest, 2003,123(4): 1112-1118.
[23]Barnes M, Houston D, Worsnop CJ, et al. A Randomized controlled trial of continuous positive airway pressure in mild obstructive sleep apnea. Am J Respir Crit Care Med,2002,165(6):773-780.
[24]Weaver TE, Laizner AM, Evans LK, et al. An instrument to measure functional status outcomes for disorders of excessive sleepiness. Sleep,1997,20 (10):835-843
[25]Yamadera W. Improvenet in excessive daytime sleepiness after surgical treatment for obstructive sleep apnea syndrome. Psychiatry Clin Neurosci,1995,49(4):213-221.
[26]Kribbs NB, Pack AI, Kline LR, et al. Effects of one night without nasal CPAP treatment on sleep and sleepiness in patients with obstructive sleep apnea. Am Rev Resp Dis,1993,147(5):1162-1168.
[27]Lam B, Sam K, Mok WYW. Randomised study of three non-surgical treatments in mild to moderate obstructive sleep apnoea. Thorax,2007, 62(4):354-359.
[28]Mok WYW, Lam CLK, Lam B. A Chinese version of the Sleep Apnea Quality of Life Index was evaluated for reliability, validity, and responsiveness. J Clin Epidemiol,2004,57(5):470-478
[29]Hui DSC, Chan JKW, Choy DKL, et al. Effects of augmented continuous positive airway pressure education andsupport on compliance and outcome in a Chinese population. Chest, 2000,117(5):1410-1416.
[30]Lacasse Y, Godbout C, Series F. Independent validation of the sleep apnoea quality of life index. Thorax,2002,57(6):483-488.
[31]Flemons W, Reimer MA. Measurement properties of the calgary sleep apnea quality of life index. Am J Respir Crit Care Med,2002, 165(2):159-164.
[32]Lacasse Y, Bureau MP, Series F. A new standardised and self-administered quality of life questionnaire specific to obstructive sleep apnoea. Thorax,2004,59(6):494-499.