肝x受体在阻塞性睡眠呼吸暂停低通气综合症患者的表达及意义
|
摘要
目的探讨肝x受体(LXR)及其表达基因胆固醇脂转运蛋白(CETP)、环氧化酶-2(COX2)在阻塞性睡眠呼吸暂停低通气综合症(OSAHS)患者中的表达及意义。
方法选取2007年8月至2008年8月经PSG确诊的OSAHS患者43例和45例非OSAHS患者;采晨血培养分离出巨噬细胞,采用RT-PCR凝胶技术检测LXR、CETP和COX2基因。
结果OSAHS患者LXR、COX2、CETP的表达高于对照组(P＜0.05);OSAHS患者LXR、COX2、CETP与其呼吸紊乱指数(AHI)呈正相关,与最低氧饱和度(LSaO2%)均呈负相关;OSAHS患者LXR、CETP的表达在轻中重分组间比较存在增强趋势(P＜0.05),COX2的表达各分组间没有明显的增强趋势(P＞0.05),其中COX2重度高于轻度(P＜0.05)。
结论OSAHS组LXR、COX2、CETP表达比对照组的表达量均有增高(p＜0.05),OSAHS患者LXR与AHI正相关,与LSaO_2%负相关,OSAHS患者COX2、CETP的表达量均与AHI正相关,与LSaO_2%负相关,OSAHS患者轻中重分组比较,LXR、CETP各分组比较P均小于0.05,有统计学意义;COX2分组间比较只有轻度和重度P小于0.05。OSAHS患者对CETP、COX2起调节作用。
Objective To study the Liver x receptor (LXR) and the gene expression of cholesterol ester transfer protein (CETP), cyclooxygenase -2 (COX2) in obstructive sleep apnea hypopnea syndrome (OSAHS) patients in the role and significance for OSAHS to provide a more favorable diagnosis, based on more accurate.
Methods Selected in August 2007 to 2008 8 menstrual PSG confirmed 43 cases of patients with OSAHS and 45 cases of non-OSAHS patients; mining morning blood culture isolated macrophages, using RT-PCR detected by gel LXR, CETP, and COX2 genes.
Results OSAHS patients with LXR, COX2, CETP expression in the control group (P <0.05); OSAHS patients with LXR, COX2, CETP and its respiratory disturbance index (AHI) was positively correlated with minimum oxygen saturation (LSaO2%) showed a negative correlation; OSAHS patients with LXR, CETP expression at light heavy division exist to strengthen the trend of inter-comparison (P <0.05), COX2 expression was not the division to strengthen the trend of significant (P> 0.05), one of COX2 severe than mild (P <0.05).
Conclusion OSAHS group LXR, COX2, CETP expression of expression than the control group by both (p <0.05), OSAHS patients LXR positively correlated with AHI of existence, and existence LSaO2% negative correlation, OSAHS patients with COX2, CETP expression in both AHI positively correlated with the existence of, and the existence LSaO2% negative correlation, OSAHS subgroup of patients with relatively light in weight, LXR, CETP comparison of the packet P <0.05, there is statistical significance; COX2 mild compared to only inter-packet and severe P less than 0.05. OSAHS patients with CETP, COX2 play a regulatory role
方法选取2007年8月至2008年8月经PSG确诊的OSAHS患者43例和45例非OSAHS患者;采晨血培养分离出巨噬细胞,采用RT-PCR凝胶技术检测LXR、CETP和COX2基因。
结果OSAHS患者LXR、COX2、CETP的表达高于对照组(P＜0.05);OSAHS患者LXR、COX2、CETP与其呼吸紊乱指数(AHI)呈正相关,与最低氧饱和度(LSaO2%)均呈负相关;OSAHS患者LXR、CETP的表达在轻中重分组间比较存在增强趋势(P＜0.05),COX2的表达各分组间没有明显的增强趋势(P＞0.05),其中COX2重度高于轻度(P＜0.05)。
结论OSAHS组LXR、COX2、CETP表达比对照组的表达量均有增高(p＜0.05),OSAHS患者LXR与AHI正相关,与LSaO_2%负相关,OSAHS患者COX2、CETP的表达量均与AHI正相关,与LSaO_2%负相关,OSAHS患者轻中重分组比较,LXR、CETP各分组比较P均小于0.05,有统计学意义;COX2分组间比较只有轻度和重度P小于0.05。OSAHS患者对CETP、COX2起调节作用。
Objective To study the Liver x receptor (LXR) and the gene expression of cholesterol ester transfer protein (CETP), cyclooxygenase -2 (COX2) in obstructive sleep apnea hypopnea syndrome (OSAHS) patients in the role and significance for OSAHS to provide a more favorable diagnosis, based on more accurate.
Methods Selected in August 2007 to 2008 8 menstrual PSG confirmed 43 cases of patients with OSAHS and 45 cases of non-OSAHS patients; mining morning blood culture isolated macrophages, using RT-PCR detected by gel LXR, CETP, and COX2 genes.
Results OSAHS patients with LXR, COX2, CETP expression in the control group (P <0.05); OSAHS patients with LXR, COX2, CETP and its respiratory disturbance index (AHI) was positively correlated with minimum oxygen saturation (LSaO2%) showed a negative correlation; OSAHS patients with LXR, CETP expression at light heavy division exist to strengthen the trend of inter-comparison (P <0.05), COX2 expression was not the division to strengthen the trend of significant (P> 0.05), one of COX2 severe than mild (P <0.05).
Conclusion OSAHS group LXR, COX2, CETP expression of expression than the control group by both (p <0.05), OSAHS patients LXR positively correlated with AHI of existence, and existence LSaO2% negative correlation, OSAHS patients with COX2, CETP expression in both AHI positively correlated with the existence of, and the existence LSaO2% negative correlation, OSAHS subgroup of patients with relatively light in weight, LXR, CETP comparison of the packet P <0.05, there is statistical significance; COX2 mild compared to only inter-packet and severe P less than 0.05. OSAHS patients with CETP, COX2 play a regulatory role
引文
[1]Young T,Palta M,Demp sey J,et al1The occurrence of sleep2disordered breathing amongmiddle2aged adults(J) 1N Engl JMed,1993;328(17):1230251
[2]Zamarron C,Gude F,Otero Y,et al1Prevalence of sleep disordered breathing and sleep apnea in 502 to 702year2old individualsla survey(J)1Resp iration,1999;66(4):3172221
[3]Schwab RJ,Goldberg AN.Upper airway assessment.Radiographec and other imaging tecgcneques.Otolaryngolynhol Clin North Am,1998,31:931-968.
[4]Bixler ED,Vgontzas AN,Lin HM,etal.The prevalence of sleep dis or dered breathing:effects of gender.[abstract]sleep,2002.22(Supp1):1o5.
[5]Peppard PE,Young T,Palta M,etal.Prospective study of the associateon between sleep—disordered breathing and hyrertensioon.N Engl J med,2002,3¨I 2:1360-1396
[6]Hasaka Y,Miyazakis,Lshikawa K,et al.The influerce of sleep position and obesity on sleep apnea.Psychiutry Clin Neurosci,2000,54:340-341.
[7]Guilleminaultc,Stoohs R,Clerk A,et al.A cause of excessive daytime sleepiness.Chest,1993,104:775-786.
[8]Ohayon MM,Guilleminault C,Priest RG,et al.Is sleep2disordered breathing an independent risk factor for hypertension in the general population(13057subjects)[J].J Psychosom Res,2000,48(6):5932601.
[9]Mary SM,Karen SL,Ho CM,et al.Serum leptin and vascular risk factors in obstructive sleep apnea[J].Chest,2000,118(3):5802586.
[10]Coughlin SR,Mawdsley L,Mugarza JA,et al.Obstructive sleep apnoea is indepently associated with an increased prevalence of metabolic syndrome[J].Eur Heart J,2004,25(9):7352741 drome[J].Eur Heart J,2004,25(9):7352741
[11]Arzt M,Young T,Finn L,et al.Association of sleep-disordered breathing and the occurrence of stroke[J].Am J Resp ir Crit Care Med,2005,172:1447-1451.,
[12]Vgontzas AN,Papanicolaou DA,Bixler EO,et al.Elevation of plasma cytokines in disorders of excessive daytime sleepiness;role of sleep disturbance and obesity.J Clin Endocrinol Metab,1997,82:1313-1316.
[13]Liu H,liu J,Xiong S,eatl.The changeof interleukin-b and tumor necrous factor in patients with apnea syndrome.J tongji Med'.Univ,2000.211.200-202
[14]Shamsmzman,AS Winnicki M,Lanfranchi P,et al.Elevated C-reactive pmtein in patients with obstructive sleep apnea.Circulation,2002,105:2462-2464.
[15]Ohga E,Tomita T,Wada H,etal.Effects of obstructive sleep apnea on circulating ICAM-1,IL-8,and MCP-1.J Appl Physiol,2003,94:179-184.
[16]Schulz R,Mahmoudi S,Hattar K,etal.Enhanced release of superoxide from polymorphonuclear neutrophils in obstructive sleep apnea.Impact of continuous positive airway pressure therapy.Am JRespir Crit Care Med,2000,162(2 Pt 1);566-570.
[17]Yamauchi M,NakanoH,Maekawa J,etal.Oxidative stress in obstructive sleep apnea.Chest,2005,127:1674-1679.
[18]黄绍光,李庆云.睡眠呼吸暂停低通气综合征的流行病学研究现状.中华全科医师杂志,2005;(4):197-295.
[19]中华医学会呼吸病学分会睡眠呼吸疾病学组.阻塞性睡眠呼吸暂停低通气综合征诊治指南.中华结核和呼吸杂志,2002;4:195-198.
[20]SehulzR,GrebemM,EiseleHJetal.ObstructivesleePapnea-related,cardiovasculardis ease·Medlin in,2006:101(4):321-7.
[21]Kasasbeh E,Chi DS,Krishnaswamy Cz Inflammatory aspects of sleep apnea and their cardiovascular consequences.South Med J.2006;99(1):58-67.
[22]Philips BCC Somers VK.Sleep disordered breathing and risk factors for cardiovascular disease.Curr Opin Pulm Med,2002;(8):516-520.
[23]Vgontzas AN,Bixler EO,Chrousos GP.Sleep apnea is a manifestation of the metabolic syndrome.Sleep Med Rev.2005;9(3):211-24.
[24]Zhang LQ,Yao WZ,Wang YZ.Relationship between obstructive sleep apnea lhypopnea syndrome and insulin resistance.:Zhonghua Nei Ke Za Zhi.2006;45(3):154-7.
[25]Libby P,Ridker PM,Maseri A.Inflammation and atherosclerosis.Circulation,2002;105:1135-1143.
[26]王轶娜,杨宇,罗荧荃et al.经鼻持续气道正压通气对阻塞性睡眠呼吸暂停低通气综合征患者血清C反应蛋白的影响.中华结核和呼吸杂志,2004:27(10):695696.
[27]王轶娜,杨宇,罗荧荃et al.经鼻持续气道正压通气对中、重度阻塞型睡眠呼吸暂停综合征患者血清细胞间豁附分子的影响.中国现代医学,2004;14(3):8996.
[28]Robinson GV,Pepperell JT,Sega HC,et al.Circulating cardiovascular risk factors in obstructive sleep apnea:data from randomized controlled trials.Thorax,2004;59:777-782.
[29]Zgierska A,Gorecka D,Radzikowska M et al.obstructive sleep apnea and risk facters for coronary artery disease.Pneumonol Alergol Po1,2000;68:238-246.
[30]周辰,张希龙,戎娟.气道正压通气治疗对阻塞性睡眠呼吸暂停患者血液高凝状态的影响.江苏医药,2004;(07):527-528.
[31]Steiner S,Jax T,Ever S et al.Altered blood rheology in obstructive sleep apnea as a mediator of cardiovascular risk.Cardiology.2005;104(2):92-6.
[32]Jianguo Li,1 Vladimir Savransky,1 Ashika Nanayakkara,1 Philip L.Smith,1Christopher P.O'Donnell,2 and Vsevolod Y.Polotsky1 Hyperlipidemia and lipid peroxidation are dependent on the severity ofchronic intermittent hypoxiaJAppl Physiol 102:557-563,2007
[33]Antonio Castrillo(?)§,Scan B.Joseph§,Chaitra Marathe§,David J.Mangelsdorf,and Peter Tontonoz(?)§Liver X Receptor-dependent Repression of Matrix Metalloproteinase-9 Expression in Macrophages~*Received for publication,December 23,2002,and in revised form,January 15,2003 Published,JBC Papers in Press,January 16,2003,DOI 10.1074/jb
[34]Lat timore J D,Wilcox I,Nakhla S.Repetitive Hypoxia Increa2ses Lipid Loading in Human Macrophages2a PotentiallyAt herogeni Effect[J].At herosclerosis ,2005 ,179 (2) :2552259.
[35] Kunjathoor, V. V., M. Febbraio, E. A. Podrez, K. J. Moore,L. Andersson, S.Koehn, J. S. Rhee, R. Silverstein, H. F. Hoff, and M. W. Freeman. 2002.Scavenger receptors class A-I/II and CD36 are the principal receptors responsible for the uptake of modified low density lipoprotein leading to lipid loading in macrophages.J. Biol. Chem. 277: 49982-49988. 4. Steinberg, D. 1997. Lewis A.Conner Memorial Lecture. Oxidative modification of LDL and atherogenesis.Circulation. 95:1062-1071.
[36] Suzuki S ,Nagai E , Taira Y,et al . In Vit ro Wear of Indirect Composite Restoratiives [J]. J Prost het Dent, 2002, 88 ( 4) :4312436.
[37] HAN Fang Obstructive sleep apnea hypopnea syndrome:a proinflammatory disorder Chinese Medical Journal 2007; 120(17):1475-1476
[38] Monica de la Pena Bravo & Laura D. Serpero & Antonia Barceló & Ferran Barbé & Alvar Agusti & David Gozal Inflammatory proteins in patients with obstructive apnea with and without daytime sleepiness sleep Breath (2007) 11:177-185 DOI 10.1007/s11325-007-0100-7
[39] Wang WJ, Nam BH, Wilson PW, et al. Association of C- reactive protein with carotid atherosclerosis in men and women: the Framingham heart study.Atheroscler Thromb Wasc 2002; 22:1512. .
[40]. Castrillo A,Joseph SB,Vaidya SA,et al.Crosstalk between LXR and toll-like receptor signaling mediates bacterial and viral antagonism of cholesterol metabolism.[J].MolCell.2003,12:805-816
[41].Tangirala RK,Bischoff ED,Joseph SB,et al.Identification of macrophage liver X receptors as inhibitors of atherosclerosis.[J].Proc Natl Acad Sci U S A.2002,99:11896-11901.
[42].Bradley MN,Tontonoz P.Lesion Macrophages Are a Key Target for the Antiatherogenic ffects f XR gonists.[J].Arteriosclerosis,Thrombosis& Vascular Biology.2005,25(1):10-11
[43]Ricote M, Valledor AF, Glass CK. Decoding transcriptional programs regulated by PPARs and LXRs in the macrophage: effects on lipid homeostasis, inflamma-tion,andatherosclerosis[J].ArteriosclerThrombVascBiol,2004,24:230-239
[44]Luo Y,Tall AR.Sterol upregulation ofhumanCETP expression in vitro and in transgenic mice by an LXR element[J].JClinInvest,2000,105:513-520
[45]唐朝克,易光辉,唐国华,王佐,王燕,刘录山等。三磷酸腺苷结合盒转运体A1在泡沫细胞胆固醇流出中的作用[J]。中国动脉硬化杂志,2003,11(4):32-36
[46]Whitney KD,WatsonMA,Goodwin B,Galardi CM,Maglich JM,Wilson JG,etal.Liver X receptor(LXR) regulation of the LXR α gene in human macrophages[J].J Biol Chem,2001,276:43 5092515
[47]Joseph SB,Castrillo A,Laffitte BA,Mangelsdorf DJ,Tontonoz P.Reciprocal regulation of inflammation and lipid metalolism by liver X receptors[J].Nature Medicine,2003,9:2132219
[48].Boche V,Millatt LJ,Fruchart JC,et al.Liver X receptors:new player in atherogenesis? Curr Opin Lipidol 14:137-143.
[49]Tall AR Luo Y.Sterol upregulation of human CETP expression in vitro and in transgenic mice by an LXR element.J Clin Invest.2000;105:513-520.
[50].Masson D,Staels B,Gautier T,et al.Cholesteryl ester transfer protein modulates the effect of liver X receptor agonists on cholesterol transport and excretion in the mouse.J.Lipid Res.2004;45:543-550.
[51]HanssonGK,Inflammationand immune response in atherosclerosis.Curt Atheroscler 1999;Rep 1:150-155)(Pasterkamp G,Schoneveld AH,Hijnen DJ,etal.Atherosclerotic arterial remodeling and the localization of macrophages andmatrix metalloproteases 1,2 and9in the human coronary artery.Atherosclerosis 2000;150:245 253.
[52].Joseph,S.B.,Castrillo,A.,Laffitte,B.A.,Mangelsdorf,D.J.,and Tontonoz,P.2003.Reciprocal regulation of inflammation and lipid metabolism by liver X receptors.Nat.Med.9:213-219.
[53].Castrillo,A.,Joseph,S.B.,Marathe,C.,Mangelsdorf,D.J.,and Tontonoz,P.2003.Liver X receptor-dependent repression of matrix metalloproteinase-9expression in macrophages.J.Biol.Chem.278:10443-10449.
[54].Terasaka,N.,et al.2005.Liver X receptor agonists inhibit tissue factor expression in macrophages.FEBS J.272:1546-1556.
[55].Ogawa,D.,et al.2005.Liver x receptor agonists inhibit cytokine-induced osteopontin expression in macrophages through interference with activator protein-1 signaling pathways.Circ.Res.96:e59-e67
[56]邹丽霞 谷卫国际内分泌代谢杂志2006年1月第26卷第1期 Intern J Endocrinol Metab,January 2006,Vol 26,No.
[57]Gomes B,Higginson IJ.Factors influencing death at home in terminally ill patients with cancer:systematic review.BMJ.,2006 332(7542):668
[58]Snipes JA,Kis B,Shelness GS,et al.Cloning and characterization of cy2clooxygenase21b(putative cyclooxygenase23) in rat.J Pharmacol Exp Ther,2005,313:6682676
[59]Poligone B,Baldwin AS.Positive and negative regulation of NF2kappaB by COX2 roles of different prostaglandins.J Biol Chem,2001,276:38658238664
[60]J Amit Benjamin and K E Lewis Sleep-disordered breathing and cardiovascular disease doi:10.1136/pgmj.2007.062836Postgrad.Med.J.2008;84;15-22
[61]Jo-Dee L.Lattimorea,b,c,~*,Ian Wilcoxa,b,Shirley Nakhlac,Matthias Langenfeldc,Wendy Jessupd,DavidS.Celermajera,b,cRepetitive hypoxia increases lipid loading in human macrophages—a potentially atherogenic effect Atherosclerosis 179(2005) 255-259
[62]Yuichiro Watanabe,Shuying Jiang,Wakako Takabe,Riuko Ohashi,Toshiya Tanaka,Expression of theLXR_Protein in Human Atherosclerotic Lesions DOI:10.1161/01.ATV.0000154489.53077.4e
[63]Naoki Terasaka1,Ayano Hiroshima1,Akiko Ariga1,Shoko Honzumi1,Tadashi Koieyama1,Toshimori Inaba2 and Toshihiko Fujiwara1 Liver X receptor agonists inhibit tissue factor expression in macrophages FEBS Journal 272(2005)1546-1556 a 2005 FEBS
[64]Whitney KD,Wats onMA,Goodwin B,et al.Liver X re2 cep t or(LXR)regulati on of the LXR α gene in human mac2 r ophages[J].J Bi ol Chem,2001,276(47):43509-43515.
[65]中华医学会呼吸病学分会睡眠呼吸疾病学组.阻塞性睡眠呼吸暂停低通气综合征诊治指南(草案).中华内科杂志,2003;42:594-597
[66]、Takemoto M,Liao JK.Pleiotropic effects of 3-hydroxy-3-methylglutaryl coenzyme a reductaseinhibitors.Arterioscler Thromb Vasc Biol.2001;21(11):1712-1719.Corsini A,Bellosta S,Baetta R,et al.New insights into the pharmacodynamic andpharmacokinetic properties of statins[J].Pharmacol Ther.1999;84(3):413-428.
[67]Jianguo Li,1Vladimir Savransky,1 Ashika Nanayakkara,1 Philip L.Smith,1 Christopher P.O'Donnell,2 and Vsevolod Y.Polotsky1Hyperlipidemia and lipid peroxidation are dependent on the severity ofchronic intermittent hypoxiaJAppl Physiol 102:557-563,2007
[68]Antonio Castrillot,Sean B.Josephs,Chaitra Marathes,David J.Mangelsdorf_,and Peter Tontonoz Liver X Receptor-dependent Repression of Matrix Metalloproteinase-9 Expression in Macrophages*Received for publication,December 23,2002,and in revised form,January 15,2003Published,JBC Papers in Press,January 16,2003,DOI 10.1074/jb
[69]HAN Fang Obstructive sleep apnea hypopnea syndrome:a proinflammatory disorder Chinese Medical Journal,2007,120(17):1475-1476
[70]Monica de la Pena Bravo & Laura D.Serpero & Antonia Barcelo & Ferran Barbe & Alvar Agusti & David Gozal Inflammatory proteins in patients with obstructive apnea with and without daytime sleepiness sleep Breath(2007)11:177-185 DOI 10.1007/s11325-007-0100-7
[71]Morales JR,Ballesteros I,Deniz JM,Hurtado O,Vivancos J,Nombela F,Lizasoain I,Castrillo A,Moro MA.Circulation.2008 Sep 30;118(14):1450-9.Epub 2008 Sep 15
[72]Joseph SB,Castrill OA,Laffitte BA,etal.Reci p r ocal regulati on of inflammati on and lipid metal olism by liver X recep t ors[J].NatureMedicine,2003,9(2):213-219.
[73]Castrillo A,Tontonoz P.Nuclear receptors in macrophage Biology:at the crossroads of lipid metabolism and inflammation[J].Annu Rev Cell Dev Biol.2004,20:455-480.
[74]Zelcer N,Tontonoz P.Liver X receptors as integrators of metabolic and inflammatory signaling[J].J Clin Invest.2006,116(3):607-614.
[75]Andreas S,Schulz R,Werner G,et al.Prevalence of obstructive sleep apnea syndrome in patients with coronary artery disease.CorArt Dis,1996 7:541-545.
[76]Koehler V Schafer H.Is obstructive sleep apnea a risk factor for myocardial infarction and cardiac arrhythmias in patients with coronary heart disease.Sleep 1996 19:283-286.
[77]黄铁群,左和鸣,尹广大等.阻塞性睡眠呼吸暂停综合征患者的血浓度和红细胞变形的变化.中华结核和呼吸杂志,2000 23(4):198.
[78]王言森,张敏,高辉等.睡眠呼吸暂停综合征患者组织纤溶酶原激活物抑制物14G/5G基因多态性分析.中华结核和呼吸杂志,2001}24(8):505.
[79]George Bokinski} Michael Miller,Kenneth Ault et al.Spontaneous platele tactivation and aggregation during obstructive sleep apnea and its response tot herapy with nasal continuous positive airway pressure.Chest} 1995,108:625-630.
[80]Nomiyama T,Bruemmer D.Liver X receptors as therapeutic targets in metabolism and atherosclerosis[J].Curr Atheroscler Rep.2008,10(1):88-95.
[81]唐朝克,贺修胜,易光辉,等.肝X受体α在泡沫细胞胆固醇流出中的调控作用[J].生物化学与生物物理进展,2003,30(6):940-944.
[82]唐朝克,杨永宗,易光辉,等.三磷酸腺苷结合盒转运体A1在THP-1巨噬细胞源性泡沫细胞胆固醇流出中的作用[J].中国病理生理杂志,2003,19(8):1084-1088.
[83]Luo Y,Tall AR.Sterol up regulation of human CETP extp ression in vitro and in vivo in transgenic mice by an LXR element[J].J Clin Invest,2000,105(4):513-520
[84]Ricote M,Valledor AF,Glass CK.Decoding transcri p2 tional programs regulated by PPARs and LXRs in the mac2 rophage:effects on li p id homeostasis,inflammati on,and atherosclerosis[J].Arteri oscler Thromb Vasc Bi ol,2004,24(2):230-239.
[85]Luo Y,Tall AR.Sterol up regulati on of human CETP excp ression in vitro and in transgenicmice by an LXR element
[86]McNicholas WT.Prog Cardiovasc Dis.2009 Mar-Apr;51(5):392-9
[87]Gomes B,Higginson IJ.BMJ.2006 Mar 4;332(7540):515-21.Epub 2006 Feb 8.Review.Erratum in:BMJ.2006 Apr 29;332(7548):1012
[2]Zamarron C,Gude F,Otero Y,et al1Prevalence of sleep disordered breathing and sleep apnea in 502 to 702year2old individualsla survey(J)1Resp iration,1999;66(4):3172221
[3]Schwab RJ,Goldberg AN.Upper airway assessment.Radiographec and other imaging tecgcneques.Otolaryngolynhol Clin North Am,1998,31:931-968.
[4]Bixler ED,Vgontzas AN,Lin HM,etal.The prevalence of sleep dis or dered breathing:effects of gender.[abstract]sleep,2002.22(Supp1):1o5.
[5]Peppard PE,Young T,Palta M,etal.Prospective study of the associateon between sleep—disordered breathing and hyrertensioon.N Engl J med,2002,3¨I 2:1360-1396
[6]Hasaka Y,Miyazakis,Lshikawa K,et al.The influerce of sleep position and obesity on sleep apnea.Psychiutry Clin Neurosci,2000,54:340-341.
[7]Guilleminaultc,Stoohs R,Clerk A,et al.A cause of excessive daytime sleepiness.Chest,1993,104:775-786.
[8]Ohayon MM,Guilleminault C,Priest RG,et al.Is sleep2disordered breathing an independent risk factor for hypertension in the general population(13057subjects)[J].J Psychosom Res,2000,48(6):5932601.
[9]Mary SM,Karen SL,Ho CM,et al.Serum leptin and vascular risk factors in obstructive sleep apnea[J].Chest,2000,118(3):5802586.
[10]Coughlin SR,Mawdsley L,Mugarza JA,et al.Obstructive sleep apnoea is indepently associated with an increased prevalence of metabolic syndrome[J].Eur Heart J,2004,25(9):7352741 drome[J].Eur Heart J,2004,25(9):7352741
[11]Arzt M,Young T,Finn L,et al.Association of sleep-disordered breathing and the occurrence of stroke[J].Am J Resp ir Crit Care Med,2005,172:1447-1451.,
[12]Vgontzas AN,Papanicolaou DA,Bixler EO,et al.Elevation of plasma cytokines in disorders of excessive daytime sleepiness;role of sleep disturbance and obesity.J Clin Endocrinol Metab,1997,82:1313-1316.
[13]Liu H,liu J,Xiong S,eatl.The changeof interleukin-b and tumor necrous factor in patients with apnea syndrome.J tongji Med'.Univ,2000.211.200-202
[14]Shamsmzman,AS Winnicki M,Lanfranchi P,et al.Elevated C-reactive pmtein in patients with obstructive sleep apnea.Circulation,2002,105:2462-2464.
[15]Ohga E,Tomita T,Wada H,etal.Effects of obstructive sleep apnea on circulating ICAM-1,IL-8,and MCP-1.J Appl Physiol,2003,94:179-184.
[16]Schulz R,Mahmoudi S,Hattar K,etal.Enhanced release of superoxide from polymorphonuclear neutrophils in obstructive sleep apnea.Impact of continuous positive airway pressure therapy.Am JRespir Crit Care Med,2000,162(2 Pt 1);566-570.
[17]Yamauchi M,NakanoH,Maekawa J,etal.Oxidative stress in obstructive sleep apnea.Chest,2005,127:1674-1679.
[18]黄绍光,李庆云.睡眠呼吸暂停低通气综合征的流行病学研究现状.中华全科医师杂志,2005;(4):197-295.
[19]中华医学会呼吸病学分会睡眠呼吸疾病学组.阻塞性睡眠呼吸暂停低通气综合征诊治指南.中华结核和呼吸杂志,2002;4:195-198.
[20]SehulzR,GrebemM,EiseleHJetal.ObstructivesleePapnea-related,cardiovasculardis ease·Medlin in,2006:101(4):321-7.
[21]Kasasbeh E,Chi DS,Krishnaswamy Cz Inflammatory aspects of sleep apnea and their cardiovascular consequences.South Med J.2006;99(1):58-67.
[22]Philips BCC Somers VK.Sleep disordered breathing and risk factors for cardiovascular disease.Curr Opin Pulm Med,2002;(8):516-520.
[23]Vgontzas AN,Bixler EO,Chrousos GP.Sleep apnea is a manifestation of the metabolic syndrome.Sleep Med Rev.2005;9(3):211-24.
[24]Zhang LQ,Yao WZ,Wang YZ.Relationship between obstructive sleep apnea lhypopnea syndrome and insulin resistance.:Zhonghua Nei Ke Za Zhi.2006;45(3):154-7.
[25]Libby P,Ridker PM,Maseri A.Inflammation and atherosclerosis.Circulation,2002;105:1135-1143.
[26]王轶娜,杨宇,罗荧荃et al.经鼻持续气道正压通气对阻塞性睡眠呼吸暂停低通气综合征患者血清C反应蛋白的影响.中华结核和呼吸杂志,2004:27(10):695696.
[27]王轶娜,杨宇,罗荧荃et al.经鼻持续气道正压通气对中、重度阻塞型睡眠呼吸暂停综合征患者血清细胞间豁附分子的影响.中国现代医学,2004;14(3):8996.
[28]Robinson GV,Pepperell JT,Sega HC,et al.Circulating cardiovascular risk factors in obstructive sleep apnea:data from randomized controlled trials.Thorax,2004;59:777-782.
[29]Zgierska A,Gorecka D,Radzikowska M et al.obstructive sleep apnea and risk facters for coronary artery disease.Pneumonol Alergol Po1,2000;68:238-246.
[30]周辰,张希龙,戎娟.气道正压通气治疗对阻塞性睡眠呼吸暂停患者血液高凝状态的影响.江苏医药,2004;(07):527-528.
[31]Steiner S,Jax T,Ever S et al.Altered blood rheology in obstructive sleep apnea as a mediator of cardiovascular risk.Cardiology.2005;104(2):92-6.
[32]Jianguo Li,1 Vladimir Savransky,1 Ashika Nanayakkara,1 Philip L.Smith,1Christopher P.O'Donnell,2 and Vsevolod Y.Polotsky1 Hyperlipidemia and lipid peroxidation are dependent on the severity ofchronic intermittent hypoxiaJAppl Physiol 102:557-563,2007
[33]Antonio Castrillo(?)§,Scan B.Joseph§,Chaitra Marathe§,David J.Mangelsdorf,and Peter Tontonoz(?)§Liver X Receptor-dependent Repression of Matrix Metalloproteinase-9 Expression in Macrophages~*Received for publication,December 23,2002,and in revised form,January 15,2003 Published,JBC Papers in Press,January 16,2003,DOI 10.1074/jb
[34]Lat timore J D,Wilcox I,Nakhla S.Repetitive Hypoxia Increa2ses Lipid Loading in Human Macrophages2a PotentiallyAt herogeni Effect[J].At herosclerosis ,2005 ,179 (2) :2552259.
[35] Kunjathoor, V. V., M. Febbraio, E. A. Podrez, K. J. Moore,L. Andersson, S.Koehn, J. S. Rhee, R. Silverstein, H. F. Hoff, and M. W. Freeman. 2002.Scavenger receptors class A-I/II and CD36 are the principal receptors responsible for the uptake of modified low density lipoprotein leading to lipid loading in macrophages.J. Biol. Chem. 277: 49982-49988. 4. Steinberg, D. 1997. Lewis A.Conner Memorial Lecture. Oxidative modification of LDL and atherogenesis.Circulation. 95:1062-1071.
[36] Suzuki S ,Nagai E , Taira Y,et al . In Vit ro Wear of Indirect Composite Restoratiives [J]. J Prost het Dent, 2002, 88 ( 4) :4312436.
[37] HAN Fang Obstructive sleep apnea hypopnea syndrome:a proinflammatory disorder Chinese Medical Journal 2007; 120(17):1475-1476
[38] Monica de la Pena Bravo & Laura D. Serpero & Antonia Barceló & Ferran Barbé & Alvar Agusti & David Gozal Inflammatory proteins in patients with obstructive apnea with and without daytime sleepiness sleep Breath (2007) 11:177-185 DOI 10.1007/s11325-007-0100-7
[39] Wang WJ, Nam BH, Wilson PW, et al. Association of C- reactive protein with carotid atherosclerosis in men and women: the Framingham heart study.Atheroscler Thromb Wasc 2002; 22:1512. .
[40]. Castrillo A,Joseph SB,Vaidya SA,et al.Crosstalk between LXR and toll-like receptor signaling mediates bacterial and viral antagonism of cholesterol metabolism.[J].MolCell.2003,12:805-816
[41].Tangirala RK,Bischoff ED,Joseph SB,et al.Identification of macrophage liver X receptors as inhibitors of atherosclerosis.[J].Proc Natl Acad Sci U S A.2002,99:11896-11901.
[42].Bradley MN,Tontonoz P.Lesion Macrophages Are a Key Target for the Antiatherogenic ffects f XR gonists.[J].Arteriosclerosis,Thrombosis& Vascular Biology.2005,25(1):10-11
[43]Ricote M, Valledor AF, Glass CK. Decoding transcriptional programs regulated by PPARs and LXRs in the macrophage: effects on lipid homeostasis, inflamma-tion,andatherosclerosis[J].ArteriosclerThrombVascBiol,2004,24:230-239
[44]Luo Y,Tall AR.Sterol upregulation ofhumanCETP expression in vitro and in transgenic mice by an LXR element[J].JClinInvest,2000,105:513-520
[45]唐朝克,易光辉,唐国华,王佐,王燕,刘录山等。三磷酸腺苷结合盒转运体A1在泡沫细胞胆固醇流出中的作用[J]。中国动脉硬化杂志,2003,11(4):32-36
[46]Whitney KD,WatsonMA,Goodwin B,Galardi CM,Maglich JM,Wilson JG,etal.Liver X receptor(LXR) regulation of the LXR α gene in human macrophages[J].J Biol Chem,2001,276:43 5092515
[47]Joseph SB,Castrillo A,Laffitte BA,Mangelsdorf DJ,Tontonoz P.Reciprocal regulation of inflammation and lipid metalolism by liver X receptors[J].Nature Medicine,2003,9:2132219
[48].Boche V,Millatt LJ,Fruchart JC,et al.Liver X receptors:new player in atherogenesis? Curr Opin Lipidol 14:137-143.
[49]Tall AR Luo Y.Sterol upregulation of human CETP expression in vitro and in transgenic mice by an LXR element.J Clin Invest.2000;105:513-520.
[50].Masson D,Staels B,Gautier T,et al.Cholesteryl ester transfer protein modulates the effect of liver X receptor agonists on cholesterol transport and excretion in the mouse.J.Lipid Res.2004;45:543-550.
[51]HanssonGK,Inflammationand immune response in atherosclerosis.Curt Atheroscler 1999;Rep 1:150-155)(Pasterkamp G,Schoneveld AH,Hijnen DJ,etal.Atherosclerotic arterial remodeling and the localization of macrophages andmatrix metalloproteases 1,2 and9in the human coronary artery.Atherosclerosis 2000;150:245 253.
[52].Joseph,S.B.,Castrillo,A.,Laffitte,B.A.,Mangelsdorf,D.J.,and Tontonoz,P.2003.Reciprocal regulation of inflammation and lipid metabolism by liver X receptors.Nat.Med.9:213-219.
[53].Castrillo,A.,Joseph,S.B.,Marathe,C.,Mangelsdorf,D.J.,and Tontonoz,P.2003.Liver X receptor-dependent repression of matrix metalloproteinase-9expression in macrophages.J.Biol.Chem.278:10443-10449.
[54].Terasaka,N.,et al.2005.Liver X receptor agonists inhibit tissue factor expression in macrophages.FEBS J.272:1546-1556.
[55].Ogawa,D.,et al.2005.Liver x receptor agonists inhibit cytokine-induced osteopontin expression in macrophages through interference with activator protein-1 signaling pathways.Circ.Res.96:e59-e67
[56]邹丽霞 谷卫国际内分泌代谢杂志2006年1月第26卷第1期 Intern J Endocrinol Metab,January 2006,Vol 26,No.
[57]Gomes B,Higginson IJ.Factors influencing death at home in terminally ill patients with cancer:systematic review.BMJ.,2006 332(7542):668
[58]Snipes JA,Kis B,Shelness GS,et al.Cloning and characterization of cy2clooxygenase21b(putative cyclooxygenase23) in rat.J Pharmacol Exp Ther,2005,313:6682676
[59]Poligone B,Baldwin AS.Positive and negative regulation of NF2kappaB by COX2 roles of different prostaglandins.J Biol Chem,2001,276:38658238664
[60]J Amit Benjamin and K E Lewis Sleep-disordered breathing and cardiovascular disease doi:10.1136/pgmj.2007.062836Postgrad.Med.J.2008;84;15-22
[61]Jo-Dee L.Lattimorea,b,c,~*,Ian Wilcoxa,b,Shirley Nakhlac,Matthias Langenfeldc,Wendy Jessupd,DavidS.Celermajera,b,cRepetitive hypoxia increases lipid loading in human macrophages—a potentially atherogenic effect Atherosclerosis 179(2005) 255-259
[62]Yuichiro Watanabe,Shuying Jiang,Wakako Takabe,Riuko Ohashi,Toshiya Tanaka,Expression of theLXR_Protein in Human Atherosclerotic Lesions DOI:10.1161/01.ATV.0000154489.53077.4e
[63]Naoki Terasaka1,Ayano Hiroshima1,Akiko Ariga1,Shoko Honzumi1,Tadashi Koieyama1,Toshimori Inaba2 and Toshihiko Fujiwara1 Liver X receptor agonists inhibit tissue factor expression in macrophages FEBS Journal 272(2005)1546-1556 a 2005 FEBS
[64]Whitney KD,Wats onMA,Goodwin B,et al.Liver X re2 cep t or(LXR)regulati on of the LXR α gene in human mac2 r ophages[J].J Bi ol Chem,2001,276(47):43509-43515.
[65]中华医学会呼吸病学分会睡眠呼吸疾病学组.阻塞性睡眠呼吸暂停低通气综合征诊治指南(草案).中华内科杂志,2003;42:594-597
[66]、Takemoto M,Liao JK.Pleiotropic effects of 3-hydroxy-3-methylglutaryl coenzyme a reductaseinhibitors.Arterioscler Thromb Vasc Biol.2001;21(11):1712-1719.Corsini A,Bellosta S,Baetta R,et al.New insights into the pharmacodynamic andpharmacokinetic properties of statins[J].Pharmacol Ther.1999;84(3):413-428.
[67]Jianguo Li,1Vladimir Savransky,1 Ashika Nanayakkara,1 Philip L.Smith,1 Christopher P.O'Donnell,2 and Vsevolod Y.Polotsky1Hyperlipidemia and lipid peroxidation are dependent on the severity ofchronic intermittent hypoxiaJAppl Physiol 102:557-563,2007
[68]Antonio Castrillot,Sean B.Josephs,Chaitra Marathes,David J.Mangelsdorf_,and Peter Tontonoz Liver X Receptor-dependent Repression of Matrix Metalloproteinase-9 Expression in Macrophages*Received for publication,December 23,2002,and in revised form,January 15,2003Published,JBC Papers in Press,January 16,2003,DOI 10.1074/jb
[69]HAN Fang Obstructive sleep apnea hypopnea syndrome:a proinflammatory disorder Chinese Medical Journal,2007,120(17):1475-1476
[70]Monica de la Pena Bravo & Laura D.Serpero & Antonia Barcelo & Ferran Barbe & Alvar Agusti & David Gozal Inflammatory proteins in patients with obstructive apnea with and without daytime sleepiness sleep Breath(2007)11:177-185 DOI 10.1007/s11325-007-0100-7
[71]Morales JR,Ballesteros I,Deniz JM,Hurtado O,Vivancos J,Nombela F,Lizasoain I,Castrillo A,Moro MA.Circulation.2008 Sep 30;118(14):1450-9.Epub 2008 Sep 15
[72]Joseph SB,Castrill OA,Laffitte BA,etal.Reci p r ocal regulati on of inflammati on and lipid metal olism by liver X recep t ors[J].NatureMedicine,2003,9(2):213-219.
[73]Castrillo A,Tontonoz P.Nuclear receptors in macrophage Biology:at the crossroads of lipid metabolism and inflammation[J].Annu Rev Cell Dev Biol.2004,20:455-480.
[74]Zelcer N,Tontonoz P.Liver X receptors as integrators of metabolic and inflammatory signaling[J].J Clin Invest.2006,116(3):607-614.
[75]Andreas S,Schulz R,Werner G,et al.Prevalence of obstructive sleep apnea syndrome in patients with coronary artery disease.CorArt Dis,1996 7:541-545.
[76]Koehler V Schafer H.Is obstructive sleep apnea a risk factor for myocardial infarction and cardiac arrhythmias in patients with coronary heart disease.Sleep 1996 19:283-286.
[77]黄铁群,左和鸣,尹广大等.阻塞性睡眠呼吸暂停综合征患者的血浓度和红细胞变形的变化.中华结核和呼吸杂志,2000 23(4):198.
[78]王言森,张敏,高辉等.睡眠呼吸暂停综合征患者组织纤溶酶原激活物抑制物14G/5G基因多态性分析.中华结核和呼吸杂志,2001}24(8):505.
[79]George Bokinski} Michael Miller,Kenneth Ault et al.Spontaneous platele tactivation and aggregation during obstructive sleep apnea and its response tot herapy with nasal continuous positive airway pressure.Chest} 1995,108:625-630.
[80]Nomiyama T,Bruemmer D.Liver X receptors as therapeutic targets in metabolism and atherosclerosis[J].Curr Atheroscler Rep.2008,10(1):88-95.
[81]唐朝克,贺修胜,易光辉,等.肝X受体α在泡沫细胞胆固醇流出中的调控作用[J].生物化学与生物物理进展,2003,30(6):940-944.
[82]唐朝克,杨永宗,易光辉,等.三磷酸腺苷结合盒转运体A1在THP-1巨噬细胞源性泡沫细胞胆固醇流出中的作用[J].中国病理生理杂志,2003,19(8):1084-1088.
[83]Luo Y,Tall AR.Sterol up regulation of human CETP extp ression in vitro and in vivo in transgenic mice by an LXR element[J].J Clin Invest,2000,105(4):513-520
[84]Ricote M,Valledor AF,Glass CK.Decoding transcri p2 tional programs regulated by PPARs and LXRs in the mac2 rophage:effects on li p id homeostasis,inflammati on,and atherosclerosis[J].Arteri oscler Thromb Vasc Bi ol,2004,24(2):230-239.
[85]Luo Y,Tall AR.Sterol up regulati on of human CETP excp ression in vitro and in transgenicmice by an LXR element
[86]McNicholas WT.Prog Cardiovasc Dis.2009 Mar-Apr;51(5):392-9
[87]Gomes B,Higginson IJ.BMJ.2006 Mar 4;332(7540):515-21.Epub 2006 Feb 8.Review.Erratum in:BMJ.2006 Apr 29;332(7548):1012