阻塞性睡眠呼吸暂停低通气综合征（OSAHS）合并2型糖尿病患者血NO、ET-1测定及其相关性
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摘要
目的:近年研究表明,阻塞性睡眠呼吸暂停低通气综合征(Obstructive sleepapnea hypopnea syndrome,OSAHS)已成为高血压、不稳定型心绞痛、心肌梗死、脑梗死的独立危险因素。OSAHS患者夜间频繁的低氧血症影响血管舒缩物质的平衡,由此导致血管内环境的失衡和血管内皮细胞受损:糖尿病(DiabetesMellitus,DM)患者血糖升高同样可以导致血管内环境的失衡和血管内皮细胞受损;OSAHS合并2型糖尿病的患者是否会加重血管内皮细胞受损程度,增加心脑血管疾病发病率尚不明确。本课题通过检测OSAHS合并2型糖尿病患者血清一氧化氮(NO)、血浆内皮素-1(ET-1)间接代表血管内皮细胞功能的指标,进行血管内皮细胞功能失调与OSAHS合并2型糖尿病患者相关性的探讨。对临床进行血管内皮保护提供理论根据。
方法:
1.选择OSAHS患者20例,患者年龄25～63(43.65±9.11)岁,体重指数26.37±3.26 kg/M~2。无糖尿病病史,空腹血糖正常。所有患者均有夜间睡眠中打鼾、呼吸暂停及白天嗜睡病史,并经纤维鼻咽喉镜检和多导睡眠仪(polysomnography,PSG)监测确诊。OSAHS的诊断按照中华医学会耳鼻咽喉科学分会、中华耳鼻咽喉科学杂志编委会2002年杭州会议关于阻塞性睡眠呼吸暂停低通气综合征的诊断标准,即睡眠呼吸暂停低通气指数(apnea hypopnea indexAHI,平均每小时睡眠中的呼吸暂停加上低通气次数)＞5次/h。呼吸暂停指睡眠过程中口鼻呼吸气流均停止10s以上,低通气指睡眠过程中呼吸气流强度较基础水平降低50%以上并伴有血氧饱和度较基础水平下降＞4%。
2.选择2型糖尿病患者18例,患者年龄21～60(46.28±10.98)岁,体重指数25.58±3.16 kg/M~2。所有患者均检查空腹血糖,按照1999年WHO糖尿病诊断标准符合2型糖尿病诊断。即空腹血糖≥7.0mmol/L。经询问病史及行睡眠监测仪筛检排除OSAHS诊断。
3.选择OSAHS合并2型糖尿病患者13例,年龄30～69(48.69±11.69)岁,体重指数27.76±3.15 kg/m~2,经询问病史及行纤维鼻咽喉镜检和多导睡眠仪监测,符合OSAHS诊断,并检测空腹血糖符合2型糖尿病诊断标准。所有研究对象均除外高血压、慢性肺部病变、神经肌肉疾病、甲状腺疾病及其他内分泌疾病、营养代谢疾病、冠心病、脑血管意外等其他全身疾病。
所有入选者在睡眠监测结束,晨醒10分钟内抽取空腹静脉血6ml,分别应用放射免疫法检测血浆ET-1水平及硝酸酶还原法检测血清NO水平。并应用快速血糖仪检测血糖。所有资料均应用SPSS11.5统计软件进行统计学处理,记量资料以(?)±S表示,采用独立样本t检验和方差分析,两变量间的相关性采用直线相关分析,计数资料采用χ~2检验。P＜0.05表示有统计学意义。
结果:
1、OSAHS合并2型糖尿病组与OSAHS组患者比较血浆ET-1浓度升高,血清NO浓度、NO/ET-1比值降低。P＜0.05,具有统计学意义。
2、OSAHS合并2型糖尿病组与糖尿病组患者比较血浆ET-1浓度升高,血清NO浓度、NO/ET-1比值降低。P＜0.05,具有统计学意义。
3、直线相关分析显示:在OSAHS合并2型糖尿病组及糖尿病组,血浆ET-1水平与血糖呈正相关(r=0.678和r=0.729),血清NO水平与血糖呈负相关(r=-0.600和r=-0.586)。在OSAHS组血浆ET-1水平与睡眠呼吸监测指标AHI呈正相关(r=0.820),血清NO水平与AHI呈负相关(r=-0.734)。在OSAHS合并2型糖尿病组血浆ET-1水平与AHI呈正相关(r=-0.629),血清NO水平与AHI相关性较差(r=-0.205)。
结论:
1.OSAHS合并2型糖尿病患者与OSAHS患者和糖尿病患者比较,血浆ET-1浓度升高,血清NO浓度、NO/ET-1比值降低。具有统计学意义。说明OSAHS合并2型糖尿病患者血管内皮受损程度更加严重。
2.糖尿病患者血浆ET-1水平与血糖呈正相关(r=0.729),血清NO水平与血糖呈负相关(r=-0.586)。
3.OSAHS患者血浆ET-1水平与AHI呈正相关(r=0.820),血清NO水平与AHI呈负相关(r=-0.734)。
4.OSAHS合并2型糖尿病患者血浆ET-1水平与血糖呈正相关(r=0.678),血清NO水平与血糖呈负相关(r=-0.600)。血浆ET-1水平与AHI呈正相关(r=0.629),血清NO水平与AHI相关性较差(r=-0.205),可能受血糖影响有关。
Objective:Many researches have investigated that OSAHS has become an independent dangerous factor of the hypertension,unsteady angina pectoris and cerebral embolism.The research indicated the continual hypoxemia in nighttime of OSAHS affects the balance of the vasoconstrictive s abstance,thereout inducing the unbalance of internal environment of blood vessel and the blood vessel's endodermis cells are damaged.The arising of blood sugar in Diabetes patients may induce the unbalance of internal environment of blood vessel and the injury of the blood vessel's endodermis cells,too.It is undefined that the injury of the blood vessel's endodermis cells and the disease of blood vessel are or aren't raised.This task proceed a discussion about the relationship between the unbalance of internal environment of blood vessel and OSAHS with 2 Diabetes through detecting nitric oxide(NO), Endothelin-1(ET-1) of OSAHS with 2 Diabetes patients' vein blood.It will provide one theoretical base for protection of the blood vessel's endodermis.
Method:
1.20 patients with OSAHS were selected,age:25-63(43.65±9.11) years old, BMI:26.37±3.26kg/M~2.The level of fasting blood sugar is normal in patients. OSAHS patients all with nocturnal snoring,apnea and excessive daytime sleepiness syndrome were diagnosed by fibrolaryngoscope and polysomnography(PSG).Including criteria for the present study were apnea-hypopnea index(AHI)＞5/h for OSAHS patients.Apnea was defined as an absence of airflow far more than 10s,and hypopnea was defined as over 50%reduction of airflow associated with a reduction of oxygen saturation by 4%from baseline.
2.18 patients with 2 Diabetes were selected,age:21-60(46.28±10.98) years old,BMI:25.58±3.16kg/M~2.The level of fasting blood sugar is≥7.0mmol/L in patients.Patients all were diagnosed.OSAHS were excluded by polysomnography(PSG).
3.13 patients with OSAHS associated 2 Diabetes were selected,age:30-69(48.69±11.69) years old,BMI:27.76±3.15kg/M~2.Patients all were diagnosed by fibrolaryngoscope and PSG and fasting blood sugar.
Fasting venous blood were obtained from all observed subjects after PSG within the following 10minutes in the next morning.Plasma ET-1 and serum NO concentrations were measured by radioimmunoassay and nitrate reductase method respectively.And fasting blood sugar is measured.Differences in parameters were assessed by software SPSS 11.5,T-test andχ~2-test were adopted.Furthermore,linear correlations were performed in every pair variances.
Results:
1.The level of plasma ET-1 of patients with OSAHS associated 2 Diabetes was higher,serum NO and NO/ET-1 were lower than the patients with OSAHS.There was statistical significance(P＜0.05).
2.The level of plasma ET-1 of patients with OSAHS associated 2 Diabetes was higher,serum NO and NO/ET-1 were lower than the patients with 2 Diabetes.There was statistical significance(P＜0.05).
3.The linear correlation was found:the plasma ET-1 level was correlated positively with fasting blood sugar(r=0.678,r=0.729),the serum NO level was correlated negatively with fasting blood sugar(r=-0.600,r=-0.586) in OSAHS associated 2 Diabetes and Diabetes patients.The plasma ET-1 level was correlated positively with AHI(r=0.820),the serum NO level was correlated negatively with AHI(r=-0.734) in OSAHS patients.The plasma ET-1 level was correlated positively with AHI(r=0.629),the serum NO level wasn't correlated with AHI(r=-0.205) in OSAHS associated 2 Diabetes patients.
Conclusions:
1.The level of plasma ET-1 of patients with OSAHS associated 2 Diabetes was higher,serum NO and NO/ET-1 were lower than the patients with OSAHS and Diabetes.There was statistical significance.To demonstrate that the injury of the blood vessel's endodermis was more serious in OSAHS associated 2 Diabetes patients.
2.The plasma ET-1 level was correlated positively with fasting blood sugar(r=0.729),the serum NO level was correlated negatively with fasting blood sugar(r=-0.586) in Diabetes patients.
3.The plasma ET-1 level was correlated positively with AHI(r=0.820),the serum NO level was correlated negatively with AHI(r=-0.734) in OSAHS patients.
4.The plasma ET-1 level was correlated positively with fasting blood sugar(r=0.678),the serum NO level was correlated negatively with fasting blood sugar(r=-0.600),the plasma ET-1 level was correlated positively with AHI(r=0.629), the serum NO level wasn't correlated with AHI(r=-0.205) in OSAHS associated 2 Diabetes patients.It was correlated probably with blood sugar.
方法:
1.选择OSAHS患者20例,患者年龄25～63(43.65±9.11)岁,体重指数26.37±3.26 kg/M~2。无糖尿病病史,空腹血糖正常。所有患者均有夜间睡眠中打鼾、呼吸暂停及白天嗜睡病史,并经纤维鼻咽喉镜检和多导睡眠仪(polysomnography,PSG)监测确诊。OSAHS的诊断按照中华医学会耳鼻咽喉科学分会、中华耳鼻咽喉科学杂志编委会2002年杭州会议关于阻塞性睡眠呼吸暂停低通气综合征的诊断标准,即睡眠呼吸暂停低通气指数(apnea hypopnea indexAHI,平均每小时睡眠中的呼吸暂停加上低通气次数)＞5次/h。呼吸暂停指睡眠过程中口鼻呼吸气流均停止10s以上,低通气指睡眠过程中呼吸气流强度较基础水平降低50%以上并伴有血氧饱和度较基础水平下降＞4%。
2.选择2型糖尿病患者18例,患者年龄21～60(46.28±10.98)岁,体重指数25.58±3.16 kg/M~2。所有患者均检查空腹血糖,按照1999年WHO糖尿病诊断标准符合2型糖尿病诊断。即空腹血糖≥7.0mmol/L。经询问病史及行睡眠监测仪筛检排除OSAHS诊断。
3.选择OSAHS合并2型糖尿病患者13例,年龄30～69(48.69±11.69)岁,体重指数27.76±3.15 kg/m~2,经询问病史及行纤维鼻咽喉镜检和多导睡眠仪监测,符合OSAHS诊断,并检测空腹血糖符合2型糖尿病诊断标准。所有研究对象均除外高血压、慢性肺部病变、神经肌肉疾病、甲状腺疾病及其他内分泌疾病、营养代谢疾病、冠心病、脑血管意外等其他全身疾病。
所有入选者在睡眠监测结束,晨醒10分钟内抽取空腹静脉血6ml,分别应用放射免疫法检测血浆ET-1水平及硝酸酶还原法检测血清NO水平。并应用快速血糖仪检测血糖。所有资料均应用SPSS11.5统计软件进行统计学处理,记量资料以(?)±S表示,采用独立样本t检验和方差分析,两变量间的相关性采用直线相关分析,计数资料采用χ~2检验。P＜0.05表示有统计学意义。
结果:
1、OSAHS合并2型糖尿病组与OSAHS组患者比较血浆ET-1浓度升高,血清NO浓度、NO/ET-1比值降低。P＜0.05,具有统计学意义。
2、OSAHS合并2型糖尿病组与糖尿病组患者比较血浆ET-1浓度升高,血清NO浓度、NO/ET-1比值降低。P＜0.05,具有统计学意义。
3、直线相关分析显示:在OSAHS合并2型糖尿病组及糖尿病组,血浆ET-1水平与血糖呈正相关(r=0.678和r=0.729),血清NO水平与血糖呈负相关(r=-0.600和r=-0.586)。在OSAHS组血浆ET-1水平与睡眠呼吸监测指标AHI呈正相关(r=0.820),血清NO水平与AHI呈负相关(r=-0.734)。在OSAHS合并2型糖尿病组血浆ET-1水平与AHI呈正相关(r=-0.629),血清NO水平与AHI相关性较差(r=-0.205)。
结论:
1.OSAHS合并2型糖尿病患者与OSAHS患者和糖尿病患者比较,血浆ET-1浓度升高,血清NO浓度、NO/ET-1比值降低。具有统计学意义。说明OSAHS合并2型糖尿病患者血管内皮受损程度更加严重。
2.糖尿病患者血浆ET-1水平与血糖呈正相关(r=0.729),血清NO水平与血糖呈负相关(r=-0.586)。
3.OSAHS患者血浆ET-1水平与AHI呈正相关(r=0.820),血清NO水平与AHI呈负相关(r=-0.734)。
4.OSAHS合并2型糖尿病患者血浆ET-1水平与血糖呈正相关(r=0.678),血清NO水平与血糖呈负相关(r=-0.600)。血浆ET-1水平与AHI呈正相关(r=0.629),血清NO水平与AHI相关性较差(r=-0.205),可能受血糖影响有关。
Objective:Many researches have investigated that OSAHS has become an independent dangerous factor of the hypertension,unsteady angina pectoris and cerebral embolism.The research indicated the continual hypoxemia in nighttime of OSAHS affects the balance of the vasoconstrictive s abstance,thereout inducing the unbalance of internal environment of blood vessel and the blood vessel's endodermis cells are damaged.The arising of blood sugar in Diabetes patients may induce the unbalance of internal environment of blood vessel and the injury of the blood vessel's endodermis cells,too.It is undefined that the injury of the blood vessel's endodermis cells and the disease of blood vessel are or aren't raised.This task proceed a discussion about the relationship between the unbalance of internal environment of blood vessel and OSAHS with 2 Diabetes through detecting nitric oxide(NO), Endothelin-1(ET-1) of OSAHS with 2 Diabetes patients' vein blood.It will provide one theoretical base for protection of the blood vessel's endodermis.
Method:
1.20 patients with OSAHS were selected,age:25-63(43.65±9.11) years old, BMI:26.37±3.26kg/M~2.The level of fasting blood sugar is normal in patients. OSAHS patients all with nocturnal snoring,apnea and excessive daytime sleepiness syndrome were diagnosed by fibrolaryngoscope and polysomnography(PSG).Including criteria for the present study were apnea-hypopnea index(AHI)＞5/h for OSAHS patients.Apnea was defined as an absence of airflow far more than 10s,and hypopnea was defined as over 50%reduction of airflow associated with a reduction of oxygen saturation by 4%from baseline.
2.18 patients with 2 Diabetes were selected,age:21-60(46.28±10.98) years old,BMI:25.58±3.16kg/M~2.The level of fasting blood sugar is≥7.0mmol/L in patients.Patients all were diagnosed.OSAHS were excluded by polysomnography(PSG).
3.13 patients with OSAHS associated 2 Diabetes were selected,age:30-69(48.69±11.69) years old,BMI:27.76±3.15kg/M~2.Patients all were diagnosed by fibrolaryngoscope and PSG and fasting blood sugar.
Fasting venous blood were obtained from all observed subjects after PSG within the following 10minutes in the next morning.Plasma ET-1 and serum NO concentrations were measured by radioimmunoassay and nitrate reductase method respectively.And fasting blood sugar is measured.Differences in parameters were assessed by software SPSS 11.5,T-test andχ~2-test were adopted.Furthermore,linear correlations were performed in every pair variances.
Results:
1.The level of plasma ET-1 of patients with OSAHS associated 2 Diabetes was higher,serum NO and NO/ET-1 were lower than the patients with OSAHS.There was statistical significance(P＜0.05).
2.The level of plasma ET-1 of patients with OSAHS associated 2 Diabetes was higher,serum NO and NO/ET-1 were lower than the patients with 2 Diabetes.There was statistical significance(P＜0.05).
3.The linear correlation was found:the plasma ET-1 level was correlated positively with fasting blood sugar(r=0.678,r=0.729),the serum NO level was correlated negatively with fasting blood sugar(r=-0.600,r=-0.586) in OSAHS associated 2 Diabetes and Diabetes patients.The plasma ET-1 level was correlated positively with AHI(r=0.820),the serum NO level was correlated negatively with AHI(r=-0.734) in OSAHS patients.The plasma ET-1 level was correlated positively with AHI(r=0.629),the serum NO level wasn't correlated with AHI(r=-0.205) in OSAHS associated 2 Diabetes patients.
Conclusions:
1.The level of plasma ET-1 of patients with OSAHS associated 2 Diabetes was higher,serum NO and NO/ET-1 were lower than the patients with OSAHS and Diabetes.There was statistical significance.To demonstrate that the injury of the blood vessel's endodermis was more serious in OSAHS associated 2 Diabetes patients.
2.The plasma ET-1 level was correlated positively with fasting blood sugar(r=0.729),the serum NO level was correlated negatively with fasting blood sugar(r=-0.586) in Diabetes patients.
3.The plasma ET-1 level was correlated positively with AHI(r=0.820),the serum NO level was correlated negatively with AHI(r=-0.734) in OSAHS patients.
4.The plasma ET-1 level was correlated positively with fasting blood sugar(r=0.678),the serum NO level was correlated negatively with fasting blood sugar(r=-0.600),the plasma ET-1 level was correlated positively with AHI(r=0.629), the serum NO level wasn't correlated with AHI(r=-0.205) in OSAHS associated 2 Diabetes patients.It was correlated probably with blood sugar.
引文
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23.郭蔚莹,刘艳,朱丹.2型糖尿病合并周围神经病变内皮素及一氧化氮水平监测.中国实验诊断学,2005:9(3):413-414.
24.林红,蔡英所.一氧化氮合酶进展[J].生物学通报,1997:32(1):10.
25.王英姿,廖风仪,韩宝玲.一氧化氮和内皮素在2型糖尿病血管病变中作用的初步探讨.天津医科大学学报,2000,6(4):443-445.
26.田蓉,平芬,高凤歧,等.阻塞性睡眠呼吸暂停低通气综合征合并高血压患者内皮素、一氧化氮及肿瘤坏死因子α的变化.中华结核和呼吸杂志,2005:28(9):641-642.
27.Redmond EM,Cahill PA,Hodges R,et al.Regulation of endothelin receptors by nitric oxide in cultured rat vascular smooth muscle cells.J Cell Physiol,1996;166(3):469-479.
28.Li H,Chen SJ,Chen YF,et al.Enhanced endothelin-1 and endothelin receptor gene expression in chronic hypoxia.J Appl Physiol,1994;77(3):1451-1459.
29.邓安春,孟祥贵,杨桦,等.OSAS患者咽组织及血浆中NO、CGRP的变化及意义.第三军医大学学报,2004:26(17):102-106.
30.Veres A,Akbari CM,Primavera J,et al.Endothelial dysfunction and the expression of endothelial nitric oxide synthetase in diabetic neuropathy,vascular disease,and foot ulceration[J].Diabetes,1998;47(3):457-463.
31.Hirata S,Yamamoto K.Post pneumonectomy empyema with bronchopleural fistula--a successful management using pedieled intercostal muscle flap on an atypical mycobacteriosis following the irradiation.Kekkaku,1991;66(1):39-44.
32.Phillips BG,Narkiewicz K,Pesek CA,et al.Effects of obstructive sleep apnea on endothelin-1 and blood pressure[J].J Hypertens,1999;17(1):61-66.
33.Schulz R,Schmidt D,Blum A,et al.Decreased plasma levels of nitric oxide derivatives in obstructive sleep apnea:response to CPAP therapy.Thorax,2000;55(12):1046-1051.
34.高永平,刘辉国.阻塞性睡眠呼吸暂停低通气综合征与内皮功能.中国医师进修杂志,2007:30(5),68-69.
1.王毓洲,黄席珍.阻塞性睡眠呼吸暂停/低通气综合症的发病机理.中国全科医学,2002;5(3):178-179.
2.Ip Mary SM,Tsang WT,Lam WK,et al.Obstructive sleep apnea syndrome:an experience in Chinese adults in Hong Kong.Chin Med J(Engl),1998;111(3):257-260.
3.Brooks B,Cistulli PA,Borkman M,et al.Obstructive sleep apnea in obese noninsulin-dependent diabetic patients:effect of continuous positive airway pressure treatment on insulin responsiveness.J Clin Endocrinal Metab,1994,79:1681-1685.
4.Gautam N,Herwald H,Hedqvist P et al.Signaling via beta(2) integrins triggers neutrophil dependent alteration in endothelial barrier function.J Exp Med,2000;191(11):1829-1839.
5.Boger RH,Bode- Boger SM,Brandes RP,et al.Dietary L-arginine reduces the progression of atherosclerosis in cholesterol-fed rabbits:comparison with lovastatin.Circulation,1997;96(4):1282-1290.
6.Inoue A,Yanagisawa M,Kimura S,et al.The human endothelin family:three structurally and pharmacologically distinct isopeptides predicted by three separate genes.Proc Natl Acad sci USA,1989;86(8):2863-2867.
7.Kitazumi K,Shiba T,Nishiki K,et al..Vasodilator effects of sarafotoxins and endothelin-1 in spontaneously hypertensive rats and rat isolated perfused mesentery.Biochem Pharmacol,1990;40(8):1843-1847.
8.Takuwa Y,Kasuya Y,Takuwa N,et al.Endothelin receptor is coupled to phospholipase C via a pertussis toxin-insensitive guanine nucleotide-binding regulatory protein in vascular smooth muscle cells.J clin Invest,1990;85(3):653-658.
9.Masaki T,Kimura S,Yanagisawa M,et al.Molecular and cellular mechanism of endothelin regulation.Implications for vascular function.Circulation,1991;84(4):1457-1468.
10.Kanagy NL,Walker BR,Nelin LD.Role of endothelin in intermittent hypoxia-induced hypertension.Hypertension,2001;37(2):511-515.
11.刘宗林.内皮塑灌流离体大鼠主动脉mgc和热休克蛋白70Mrna基因表达的增强作用.基础医学与临床,1995:15(3):40-42.
12.Boulanger C,Luscher TF.Release of endothelin fi'om the porcine aorta.Inhibition by endothelium-derived nitric oxide.J Clin Invest,1990;85(2):587-590.
13.Arai H,Hod S,Aramori I,et al.Cloning and exprssion of a cDNA encoding an endothelin receptor.Nature,1990;348(6303):730-732.
14.He J,Kryger MH,Zorick.FJ,et al.Mortality and apnea index in obstructive sleep apnea:experience in 385 male patients[J].Chest,1988;94(1):9-14.
15.Wieczorek I,Haynes WG,Webb DJ,et al.Raised plasma endothelin in unstable angina and non-Q wave myocardial infarction:Relation to cardiovascular outcome[J].Br Heart.J,1994;72(5):436-441.
16.Dyken ME,Somers VK,Yamada T,et al.Investigating the relationship between stroke and obstructive sleep apnea[J].Stroke,1996;27(3):401-407.
17.肖丹,康健,王秋月.阻塞性睡眠呼吸暂停患者睡眠时高血压的发生[J].中华结核和呼吸杂志,1998:21(11):654-657.
18.Phillips BG,Narkiewicz K,Pesek CA,et al.Effects of obstructive sleep apnea on endothelin-1 and blood pressure[J].J Hypertens,1999;17(1):61-66.
19.田蓉,平芬,高凤歧,等.阻塞性睡眠呼吸暂停低通气综合征合并高血压患者内皮素、一氧化氮及肿瘤坏死因子α的变化.中华结核和呼吸杂志,2005:28(9):641-642.
20.扬朝,张锦.阻塞性睡眠呼吸暂停低通气综合征患者血浆ET-1、NO水平的变化及nCPAP对其影响.中国老年学杂志,20C4:24(9):793-795.
21.Boulanger CM.Secondary endothelial dysfunction:hypertension and heart failure.J Mol Cell Cardiol,1999;31(1):39-49.
22.Lavie L.Obstructive sleep apnoea syndrome--an oxidative stress disorder.Sleep Med Rev,2003;7(1):35-51.
23.颜萍,张希龙,殷凯生,等.阻塞性睡眠呼吸暂停患者心脑血管血栓性疾病高危因素的观察.心脑血管病防治,2003:3(1):13-15.
24.Kawano H,Motoyama T,Hirashima O,et al.Hyperglycemia rapidly suppresses flow-mediated endothelium-dependent vasodilatien of brachial artery[J].J Am Coll Cardiol,1999;34(1):146-154.
25.郭蔚莹,刘艳,朱丹.2型糖尿病合并周围神经病变内皮素及一氧化氮水平监测.中国实验诊断学,2005:9(3):413-414.
26.王友莲,施春花,邹琳.2型糖尿病患者血浆内皮素变化及影响因素.江西医药,2001:36(2):122-120.
27.黄敬泽,张珍.血管内皮细胞、血浆内皮素值与糖尿病患者微血管病变的相关性及评估.中国糖尿病杂志,1999:7(2):70-72.
28.王中京,黄友镐.糖尿病合并血管病变血浆内皮素测定临床分析.临床内科杂志,1996:13(4):44-45.
29.李秀娟,王乐韦,毛腾淑,等.糖尿病患者血浆内皮素水平升高和临床意义.北京医药,1996:18(2):69-71.
30.Veres A,Akbafi CM,Primavera J,et al.Endothelial dysfunction and the expression of endothelial nitric oxide synthetase in diabetic neuropathy,vascular disease,and foot ulceration[J].Diabetes,1998;47(3):457-463.
31.Hirata S,Yamamoto K.Post pneumonectomy empyema with bronchopleural fistula--a successful management using pedicled intercostal muscle flap on an atypical mycobacteriosis following the irradiation.Kekkaku,1991;66(1):39-44.
32.王英姿,廖风仪,韩宝玲.一氧化氮和内皮素在2型糖尿病血管病变中作用的初步探讨.天津医科大学学报,2000:6(4):443-445.
33.林红,蔡英所.一氧化氮合酶进展[J].生物学通报,1997:32(1):10.
34.Hodgson WC,King RG.Effects of glucose,insulin or aldose reductase inhibition on reponse to endothelin-1 of aortic tings from strepotozocin induced diabetic rats[J].Br J Pharmacol,1992;106(3):644-649.
35.Young T,Palta M,Dempsey J,et al.The occurrence of sleep-disordered breathing among middle-aged adults[J].N Engl J Med,1993;328(17):1230-1235.
36.张安玉.糖尿病的流行形势及其防治的有关问题.中国慢性病预防与控制,2005:13(6):257-258.
37.Fuyuno G,Kobayashi R,Atsumi Y,et al.Relationship between diabetes mellitus-associated obstructive sleep apnea syndrome and hyperinsulinemia.Nihon Kokyuki Gakkai Zasshi,1999;37(9):694-698.
38.丁少芳.阻塞性睡眠呼吸暂停低通气综合征与内分泌疾病.心肺血管病杂志,2007:26(1):57-58.
39.Buttini M,Akeefe H,Lin C,et al.Dominant negative effects of apolipoprotein E4 revealed in transgenic models of neurodegenerative disease.Neuroscience,2000;97(2):207-210.
40.肖高辉,黄席珍.糖尿病与睡眠呼吸障碍.中华老年医学杂志,2002:21(1):12-13.
41.Stoohs RA,Facchini F,Guilleminault C.Insulin resistance and sleep-disordered breathing in healthy humans[J].Am J Respir Crit Care Med,1996;154(1):170-174.
42.Tiihonen M,Partinen M,Narvanen S.The severity of obstructive sleep apnoea is associated with insulin resistance[J].J Sleep Res,1993;2(1):56-61.
43.Meslier N,Gagnadoux F,Giraud P,et al.Impaired glucose-insulin metabolism in males with obstructive sleep apnoea syndrome[J].Eur Respir J,2003;22(1):156-160.
44.Harsh IA,Schahin SP,Radespiel-Troger M,et al.Continuous positive airway pressure treatment rapidly improves insulin sensitivity in patients with obstructive sleep apnea syndrome[J].Am J Respir Crit Care Med,2004;169(2):156-162.
45.Rosmond R,Dallman MF,Bjomtorp P.Stress-related cortisol secretion in men:relationships with abdominal obesity and endocrine,metabolic and hemodynamic abnormalities[J].J Clin Endocrinol Metab,1998;83(6):1853-1859.
46.Pasquali R,Vicennati V.The abdominal obesity phenotype and insulin resistance are associated with abnormalities of the hypothalamic-pituitary-adrenal axis in humans[J].Horm Metab Res,2000;32(11 -12):521-525.
47.Ip MS,Lam B,Chan LY,et al.Circulating nitric oxide is suppressed in obstructive sleep apnea and is reversed by nasal continuous positive airway pressure[J].Am J Respir Crit Care Med,2000;162(6):2166-2171.
48.Shichiri M,Hirata Y,Ando K,et al.Plasma endothelin levels in hypertension and chronic renal failure[J].Hypertension,1990;15(5):493-496.
2.胡仁明,朱禧星.糖尿病的病因、分类和诊断.见:陈灏珠主编.实用内科学(第12版).北京:人民卫生出版社.2005:1015-1026.
3.Young T,Palta M,Dempsey J,et al.The occurrence;of sleep-disordered breathing among middle-aged adults[J].N Engl J Med,1993;328(17):1230-1235.
4.王毓洲,黄席珍.阻塞性睡眠呼吸暂停/低通气综合症的发病机理.中国全科医学,2002:5(3);178-179.
5.Ip Mary SM,Tsang WT,Lam WK,et al.Obstructive sleep apnea syndrome:an experience in Chinese adults in Hong Kong.Chin Med J(Engl),1998;111(3):257-260.
6.Brooks B,Cistulli PA,Borkrnan M,et al.Obstructive.sleep apnea in obese noninsulin-dependent diabetic patients:effect of continuous positive airway pressure treatment on insulin responsiveness.J Clin Endocrinal Metab,1994;79(6):1681-1685.
7.Fuyuno G;Kobayashi.R,Atsumi Y,et al.Relationship between diabetes mellitus-associated obstructive sleep apnea syndrome and hyperinsulinemia.Nihon Kokyuki Gakkai Zasshi,1999;37(9):694-698.
8.丁少芳.阻塞性睡眠呼吸暂停低通气综合征与内分泌疾病.心肺血管病杂志,2007:26(1):57-58.
9.于键,苏珂.瘦素与2型糖尿病及胰岛素抵抗[J].新医学,2002:33(11):692.
10.Peltier AC,Consens FB,Sheikh K,et al.Autor.omic dysfunction in obstructive sleep apnea is associated with impaired glucose regulation[J].Sleep Med,2007;8(2):149-155.
11.Buttini M,Akeefe H,Lin C,et al.Dominant negative effects of apolipoprotein E4 revealed in transgenic models of neurodegenerative disease.Neuroscience,2000;97(2):207-210.
12.Haight JS,Djupesland PG..Nitric oxide(NO) and obstructive sleep apnea(OSA).Sleep Breath.2003;7(2):53-62.
13.Kato M,Roberts-Thomson P,Phillips BG,et al.Impairment of endothelium-dependent vasodilation of resistance vessels in patients with obstructive sleep apnea.Circulation,2000;102(21):2607-2610.
14.Boulanger CM.Secondary endothelial dysfunction:hypertension and heart-failure.J Mol Cell Cardiol,1999;31(1):39-49.
15.Kourembanas S,Marsden PA,McQuillan LP,et al.Hypoxia induces endothelin gene expression and secretion in cultured human endothelium.J Clin Invest,1991;88(3):1054-1057.
16.Lavie L.Obstructive sleep apnoea syndrome--an oxidative stress disorder.Sleep Med Rev.2003;7(1):35-51.
17.王友莲,施春花,邹琳.2型糖尿病患者血浆内皮素变化及影响因素.江西医药,2001;36(2):122-123.
18.黄敬泽,张珍.血管内皮细胞、血浆内皮素值与糖尿病患者微血管病变的相关性及评估.中国糖尿病杂志,1999;7(2):70-72.
19.王中京,黄友镐.糖尿病合并血管病变血浆内皮素测定临床分析.临床内科杂志,1996;13(4):44-45.
20.李秀娟,王乐韦,毛腾淑,等.糖尿病患者血浆内皮素水平升高和临床意义.北京医药,1996;18(2):69-71.
21.Ip MS,Lam B,Chan LY,et al.Circulating nitric oxide is suppressed in obstructive sleep apnea and is reversed by nasal continuous positive airway pressure[J].Am J Respir Crit Care Med,2000;162(6):2166-2171.
22.Hodgson WC,King RG.Effects of glucose,insulin or aldose reductase inhibition on responses to endothelin-1 of aortic rings from strepotozocin induced diabetic rats[J].Br J Pharmacol,1992;106(3):644-649.
23.郭蔚莹,刘艳,朱丹.2型糖尿病合并周围神经病变内皮素及一氧化氮水平监测.中国实验诊断学,2005:9(3):413-414.
24.林红,蔡英所.一氧化氮合酶进展[J].生物学通报,1997:32(1):10.
25.王英姿,廖风仪,韩宝玲.一氧化氮和内皮素在2型糖尿病血管病变中作用的初步探讨.天津医科大学学报,2000,6(4):443-445.
26.田蓉,平芬,高凤歧,等.阻塞性睡眠呼吸暂停低通气综合征合并高血压患者内皮素、一氧化氮及肿瘤坏死因子α的变化.中华结核和呼吸杂志,2005:28(9):641-642.
27.Redmond EM,Cahill PA,Hodges R,et al.Regulation of endothelin receptors by nitric oxide in cultured rat vascular smooth muscle cells.J Cell Physiol,1996;166(3):469-479.
28.Li H,Chen SJ,Chen YF,et al.Enhanced endothelin-1 and endothelin receptor gene expression in chronic hypoxia.J Appl Physiol,1994;77(3):1451-1459.
29.邓安春,孟祥贵,杨桦,等.OSAS患者咽组织及血浆中NO、CGRP的变化及意义.第三军医大学学报,2004:26(17):102-106.
30.Veres A,Akbari CM,Primavera J,et al.Endothelial dysfunction and the expression of endothelial nitric oxide synthetase in diabetic neuropathy,vascular disease,and foot ulceration[J].Diabetes,1998;47(3):457-463.
31.Hirata S,Yamamoto K.Post pneumonectomy empyema with bronchopleural fistula--a successful management using pedieled intercostal muscle flap on an atypical mycobacteriosis following the irradiation.Kekkaku,1991;66(1):39-44.
32.Phillips BG,Narkiewicz K,Pesek CA,et al.Effects of obstructive sleep apnea on endothelin-1 and blood pressure[J].J Hypertens,1999;17(1):61-66.
33.Schulz R,Schmidt D,Blum A,et al.Decreased plasma levels of nitric oxide derivatives in obstructive sleep apnea:response to CPAP therapy.Thorax,2000;55(12):1046-1051.
34.高永平,刘辉国.阻塞性睡眠呼吸暂停低通气综合征与内皮功能.中国医师进修杂志,2007:30(5),68-69.
1.王毓洲,黄席珍.阻塞性睡眠呼吸暂停/低通气综合症的发病机理.中国全科医学,2002;5(3):178-179.
2.Ip Mary SM,Tsang WT,Lam WK,et al.Obstructive sleep apnea syndrome:an experience in Chinese adults in Hong Kong.Chin Med J(Engl),1998;111(3):257-260.
3.Brooks B,Cistulli PA,Borkman M,et al.Obstructive sleep apnea in obese noninsulin-dependent diabetic patients:effect of continuous positive airway pressure treatment on insulin responsiveness.J Clin Endocrinal Metab,1994,79:1681-1685.
4.Gautam N,Herwald H,Hedqvist P et al.Signaling via beta(2) integrins triggers neutrophil dependent alteration in endothelial barrier function.J Exp Med,2000;191(11):1829-1839.
5.Boger RH,Bode- Boger SM,Brandes RP,et al.Dietary L-arginine reduces the progression of atherosclerosis in cholesterol-fed rabbits:comparison with lovastatin.Circulation,1997;96(4):1282-1290.
6.Inoue A,Yanagisawa M,Kimura S,et al.The human endothelin family:three structurally and pharmacologically distinct isopeptides predicted by three separate genes.Proc Natl Acad sci USA,1989;86(8):2863-2867.
7.Kitazumi K,Shiba T,Nishiki K,et al..Vasodilator effects of sarafotoxins and endothelin-1 in spontaneously hypertensive rats and rat isolated perfused mesentery.Biochem Pharmacol,1990;40(8):1843-1847.
8.Takuwa Y,Kasuya Y,Takuwa N,et al.Endothelin receptor is coupled to phospholipase C via a pertussis toxin-insensitive guanine nucleotide-binding regulatory protein in vascular smooth muscle cells.J clin Invest,1990;85(3):653-658.
9.Masaki T,Kimura S,Yanagisawa M,et al.Molecular and cellular mechanism of endothelin regulation.Implications for vascular function.Circulation,1991;84(4):1457-1468.
10.Kanagy NL,Walker BR,Nelin LD.Role of endothelin in intermittent hypoxia-induced hypertension.Hypertension,2001;37(2):511-515.
11.刘宗林.内皮塑灌流离体大鼠主动脉mgc和热休克蛋白70Mrna基因表达的增强作用.基础医学与临床,1995:15(3):40-42.
12.Boulanger C,Luscher TF.Release of endothelin fi'om the porcine aorta.Inhibition by endothelium-derived nitric oxide.J Clin Invest,1990;85(2):587-590.
13.Arai H,Hod S,Aramori I,et al.Cloning and exprssion of a cDNA encoding an endothelin receptor.Nature,1990;348(6303):730-732.
14.He J,Kryger MH,Zorick.FJ,et al.Mortality and apnea index in obstructive sleep apnea:experience in 385 male patients[J].Chest,1988;94(1):9-14.
15.Wieczorek I,Haynes WG,Webb DJ,et al.Raised plasma endothelin in unstable angina and non-Q wave myocardial infarction:Relation to cardiovascular outcome[J].Br Heart.J,1994;72(5):436-441.
16.Dyken ME,Somers VK,Yamada T,et al.Investigating the relationship between stroke and obstructive sleep apnea[J].Stroke,1996;27(3):401-407.
17.肖丹,康健,王秋月.阻塞性睡眠呼吸暂停患者睡眠时高血压的发生[J].中华结核和呼吸杂志,1998:21(11):654-657.
18.Phillips BG,Narkiewicz K,Pesek CA,et al.Effects of obstructive sleep apnea on endothelin-1 and blood pressure[J].J Hypertens,1999;17(1):61-66.
19.田蓉,平芬,高凤歧,等.阻塞性睡眠呼吸暂停低通气综合征合并高血压患者内皮素、一氧化氮及肿瘤坏死因子α的变化.中华结核和呼吸杂志,2005:28(9):641-642.
20.扬朝,张锦.阻塞性睡眠呼吸暂停低通气综合征患者血浆ET-1、NO水平的变化及nCPAP对其影响.中国老年学杂志,20C4:24(9):793-795.
21.Boulanger CM.Secondary endothelial dysfunction:hypertension and heart failure.J Mol Cell Cardiol,1999;31(1):39-49.
22.Lavie L.Obstructive sleep apnoea syndrome--an oxidative stress disorder.Sleep Med Rev,2003;7(1):35-51.
23.颜萍,张希龙,殷凯生,等.阻塞性睡眠呼吸暂停患者心脑血管血栓性疾病高危因素的观察.心脑血管病防治,2003:3(1):13-15.
24.Kawano H,Motoyama T,Hirashima O,et al.Hyperglycemia rapidly suppresses flow-mediated endothelium-dependent vasodilatien of brachial artery[J].J Am Coll Cardiol,1999;34(1):146-154.
25.郭蔚莹,刘艳,朱丹.2型糖尿病合并周围神经病变内皮素及一氧化氮水平监测.中国实验诊断学,2005:9(3):413-414.
26.王友莲,施春花,邹琳.2型糖尿病患者血浆内皮素变化及影响因素.江西医药,2001:36(2):122-120.
27.黄敬泽,张珍.血管内皮细胞、血浆内皮素值与糖尿病患者微血管病变的相关性及评估.中国糖尿病杂志,1999:7(2):70-72.
28.王中京,黄友镐.糖尿病合并血管病变血浆内皮素测定临床分析.临床内科杂志,1996:13(4):44-45.
29.李秀娟,王乐韦,毛腾淑,等.糖尿病患者血浆内皮素水平升高和临床意义.北京医药,1996:18(2):69-71.
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