阻塞性睡眠呼吸暂停低通气综合征患者认知功能的改变与血清NSE、S-100β蛋白浓度的关系探讨
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摘要
[目的]探讨血清S-100β蛋白、NSE浓度与阻塞性睡眠呼吸暂停低通气综合征(OSAHS)患者认知功能损害的关系。
[方法]OSAHS组30例,对照组20例进行多导睡眠仪(PSG)和MMSE(mini-mentalstate examination,简易精神状态量表)检查,用酶联免疫方法检测血清NSE、S-100β蛋白水平,观察患者血清NSE、S-100β蛋白浓度的变化,并探讨它与认知功能,夜间低氧和睡眠结构紊乱间的关系。
[结果]1.OSAHS组Ⅰ+Ⅱ期睡眠比例较对照组明显延长,Ⅲ+Ⅳ期睡眠和快动眼相睡眠比例均较非OSAHS组有明显减少;同时OSAHS组夜间睡眠时存在严重呼吸紊乱现象,AHI显著高于对照组,而平均血氧饱和度(%)和最低血氧饱和度(%)均显著低于对照组。
2.OSAHS患者MMSE总分明显低于对照组,其中记忆力、注意力及计算力、回忆三个方面的MMSE量表因子明显低于对照组,它们与夜间最低血氧饱和度呈正相关,与睡眠结构紊乱和呼吸紊乱指数无相关性。
3.OSAHS患者血清S-100β蛋白水平显著升高,血清NSE水平与对照相比无显著差异。
4.血清S-100β蛋白水平与MMSE总分呈显著负相关,S-100β与记忆力、注意力及计算力、回忆呈显著负相关,S-100β与最低血氧饱和度呈显著负相关,与与Ⅲ+Ⅳ期睡眠呈负相关,与Ⅰ+Ⅱ期睡眠呈正相关。
[结论]1.OSAHS患者存在明显的夜间血氧饱和度下降和睡眠结构紊乱。
2.OSAHS患者神经认知功能较正常对照组差,表现为记忆力、注意力及计算力、回忆等方面较差。主要受夜间最低血氧饱和度影响明显。
3.OSAHS患者血S-100β蛋白水平较正常组有明显升高,与认知功能的损害有一定的相关性。且血S-100β蛋白的升高与夜间低氧和睡眠结构的紊乱有相关性,提示血清S-100β蛋白有可能作为观察OSAHS患者认知功能损害的生化指标。
[Objective]:To investigate the clinical significance of S-100βand NSE in serum from cognitive impairment in patients with obstructive sleep apnea hypoventilation syndrome (OSAHS).
[Methods]:Polysomnography was administered to thirty patients with OSAHS and twenty healthy controls,all patients and controls for 7 hours at night.Early next morning blood was drawn and serum NSE and S-100βwas determined by ELISA.Then MMSE tests were conducted.the data were analysed with statistical methods.
[Results]:1.There have significant difference on AHI、Ⅰ-Ⅱsleep、Ⅲ-Ⅳsleep、lowest Sap2、mean Sap2、REM sleep duration in OSAHS patients of PSG to compare with the controls(Ⅲ+Ⅳsleep and REM sleep decreased,Ⅰ+Ⅱsleep and AHI increased,lowest Sap2 and mean Sap2 decreased).2.The score of MMSE in patients with OSAHS significantly lower than the control group.The score of memory、recall、attention and counting in patiens with OSAHS significantly lower than the control group.They are positively related to the lowest SaO_2.They had not remarkable relationship with the fragmented sleep and AHI.3.The serum S-100βlevel of the patients with OSAHS significantly higher than the controls,Serum NSE was similar in both groups.4.The serum S-100βlevel was significantly negatively correlated with the scores of MMSE,the serum S-100βlevel was significantly negatively correlated with the score of memory and the score of attention and counting and the score of recall.The serum S-100βlevel was remarkable negatively related to the lowest SaO_2 andⅢ+Ⅳsleep and positively related toⅠ+Ⅱsleep.
[Conclution]:1.The patients with OSAHS suffer from fragmented sleep and decreased arterial oxygen saturations.2.The cogonitive functions in OSAHS patients were impaired,including memory,attention and counting,recall.They are positively related to the lowest SaO_2.3.The serum S-100βlevel of the patients with OSAHS was signiticantly higher than the controls,and correlated with cognitive impairment.The serum S-100βlevel was remarkable negatively related to the lowest SaO_2 andⅢ+Ⅳsleep and positively related toⅠ+Ⅱsleep.S-100βmay play a role in the cognitive impairment in patients with OSAHS in biochemistry.
[方法]OSAHS组30例,对照组20例进行多导睡眠仪(PSG)和MMSE(mini-mentalstate examination,简易精神状态量表)检查,用酶联免疫方法检测血清NSE、S-100β蛋白水平,观察患者血清NSE、S-100β蛋白浓度的变化,并探讨它与认知功能,夜间低氧和睡眠结构紊乱间的关系。
[结果]1.OSAHS组Ⅰ+Ⅱ期睡眠比例较对照组明显延长,Ⅲ+Ⅳ期睡眠和快动眼相睡眠比例均较非OSAHS组有明显减少;同时OSAHS组夜间睡眠时存在严重呼吸紊乱现象,AHI显著高于对照组,而平均血氧饱和度(%)和最低血氧饱和度(%)均显著低于对照组。
2.OSAHS患者MMSE总分明显低于对照组,其中记忆力、注意力及计算力、回忆三个方面的MMSE量表因子明显低于对照组,它们与夜间最低血氧饱和度呈正相关,与睡眠结构紊乱和呼吸紊乱指数无相关性。
3.OSAHS患者血清S-100β蛋白水平显著升高,血清NSE水平与对照相比无显著差异。
4.血清S-100β蛋白水平与MMSE总分呈显著负相关,S-100β与记忆力、注意力及计算力、回忆呈显著负相关,S-100β与最低血氧饱和度呈显著负相关,与与Ⅲ+Ⅳ期睡眠呈负相关,与Ⅰ+Ⅱ期睡眠呈正相关。
[结论]1.OSAHS患者存在明显的夜间血氧饱和度下降和睡眠结构紊乱。
2.OSAHS患者神经认知功能较正常对照组差,表现为记忆力、注意力及计算力、回忆等方面较差。主要受夜间最低血氧饱和度影响明显。
3.OSAHS患者血S-100β蛋白水平较正常组有明显升高,与认知功能的损害有一定的相关性。且血S-100β蛋白的升高与夜间低氧和睡眠结构的紊乱有相关性,提示血清S-100β蛋白有可能作为观察OSAHS患者认知功能损害的生化指标。
[Objective]:To investigate the clinical significance of S-100βand NSE in serum from cognitive impairment in patients with obstructive sleep apnea hypoventilation syndrome (OSAHS).
[Methods]:Polysomnography was administered to thirty patients with OSAHS and twenty healthy controls,all patients and controls for 7 hours at night.Early next morning blood was drawn and serum NSE and S-100βwas determined by ELISA.Then MMSE tests were conducted.the data were analysed with statistical methods.
[Results]:1.There have significant difference on AHI、Ⅰ-Ⅱsleep、Ⅲ-Ⅳsleep、lowest Sap2、mean Sap2、REM sleep duration in OSAHS patients of PSG to compare with the controls(Ⅲ+Ⅳsleep and REM sleep decreased,Ⅰ+Ⅱsleep and AHI increased,lowest Sap2 and mean Sap2 decreased).2.The score of MMSE in patients with OSAHS significantly lower than the control group.The score of memory、recall、attention and counting in patiens with OSAHS significantly lower than the control group.They are positively related to the lowest SaO_2.They had not remarkable relationship with the fragmented sleep and AHI.3.The serum S-100βlevel of the patients with OSAHS significantly higher than the controls,Serum NSE was similar in both groups.4.The serum S-100βlevel was significantly negatively correlated with the scores of MMSE,the serum S-100βlevel was significantly negatively correlated with the score of memory and the score of attention and counting and the score of recall.The serum S-100βlevel was remarkable negatively related to the lowest SaO_2 andⅢ+Ⅳsleep and positively related toⅠ+Ⅱsleep.
[Conclution]:1.The patients with OSAHS suffer from fragmented sleep and decreased arterial oxygen saturations.2.The cogonitive functions in OSAHS patients were impaired,including memory,attention and counting,recall.They are positively related to the lowest SaO_2.3.The serum S-100βlevel of the patients with OSAHS was signiticantly higher than the controls,and correlated with cognitive impairment.The serum S-100βlevel was remarkable negatively related to the lowest SaO_2 andⅢ+Ⅳsleep and positively related toⅠ+Ⅱsleep.S-100βmay play a role in the cognitive impairment in patients with OSAHS in biochemistry.
引文
1.Hardemark HG,Ericsson N,Kotwica Z,et al.S-100 protein and ncuro- specific enolasc in CSF after experimental traumatic or focal ischemic brain damage.J Neurosurg,1989;71:727
2.Hernnann M,Jort S,Kutz S,et al.Temporal profile of release of nenrobiochemical markers of brain damage after traumatic brain injury is associated with intraeranial pathology as demonstrated in cranial computerized tomography.J Neurotrauma,2000;17:113-122
3.Fassbender K,Schmidt,Schreiner A,et al.LeaKage of brain-originated proteins in peripheral blood:temporal profile and diagnostic value in early ischemic stroke.J Neurol Sci,1997;148:101-105
4.Wainwright MS,craft JM,Griffin WS,et al.Increased susceptibility of S-100B transgenic mice to perinatal hypoxia-ischemia.AnnNeurol,2004;56:61-67
5.汤慈美,王新德.神经病学.第7卷.北京:人民军医出版社,2001;342-343
6.ohen-Zion M,Stepnowsky C,Johnson s,et al.Cognitive changes and sleep disordered breathing in elderly:differences in race.JPsychosom Res,2004,56:549-553
7.Sateia MJ.Neuropsychological impairment and quality of life in obstructive sleep apnea.Clin Chest Med,2003;24:249-259
8.Engleman HM,Kingshott Rn,MartinSE,Douglas NJ.Congnitive function in the sleep apnea/hypopnea syndrome(SAHS).sleep,2000 Jun;15;23 supple 4:s 102-s108
9.Kingshott Rn,Engleman HM,Deary IJ,et al.Does arousal frequency predict daytime function ?Eur Respir J,1998;12:1264-1270
10.Findley Lt,Barth JT,PowersDC,et al.Cognitive impairments with obstructive sleep apnea and associated hypoxemia.chest,1986;90:686-690
11.Borak J,Cieslicki JK,Koziej M,et al.Effects of CPAP treatment on psychological status in patients with severe obstrctive sleep apnea.J sleep Res,1996;5:123-127
12.彭斌,李舜伟,黄席珍,等.睡眠呼吸暂停综合症及鼾症患者时间相关电位研究.中华医学杂志,2000;80:429-431
13.LindaJ,van Eldik,Mark S,et al.The janus face of glial-derived sl00B:Beneficialk and detrimental functions in the brain.restorative Neurology and neuroscience,2003;21:97-108
14.HerrmannM,VosP,WunderlichMT,etal.Release ofglial tissue-specific oroteins afte racute stroke:Acomparative analysis of serum concentrations of protein S-100Band glial fibrillary acidic protein.Stroke,2000;31:2670-2677
15.Palmio J,PeltolaJ,Vuorinen P,et al.Normal CSF neuron-specific enolase and S-100 protein levels in patients with recent non-complicated to nic-clonic seizures.J Neurol Sci,2001;183:27-31
16.Ploy MC,Chainier D,Tran-Thi NH,et al.Integron-asso-ciated antibiotic resistance in Salmonella enterica serovar type from Asia.Antimicrob Agents Chemother,2003;47:1427-1429
17.王淮燕,郭锡熔.窒息后缺氧缺血性新生儿脐血S-100B蛋白变化的意义.实用儿科临床杂志,2006;21:916-17
18.Hu J,Van Eldik LJ.S100B induces apoptotic cell death incultured astrocytes via a nitric oxide-dependent pathway.Biochem Biophy Acta,1996;1313:239-245
19.Gozal E,row BW,SchuA,et al.Developmental differences incorticaland hippocampal vulnerability to intermittent hypoxia in the rat,Neurosci.Lett.2001;305:197-201
20.Benowitz LI,RouttenbergA.a membrance phosphoprotein associated with neural development,axonal regeneration,phospholipids metabolkism,and synaptic plasticity.Trends Neurosci,1987;10:527-532
21.Holscher C.Nitric oxide,the enigmatic neuronal messengar:its role in synaptic plasticity.Trends in Neurosci,1997;20:298-303
22.Yamada K,Noda Y,Nakayama S,et al.Role of nitric oxide in learning and memory and in monoamine metabolism in the rat brain.Bri J Pharm,1995;115:852-858
23.高东,王景周,向静.脑梗死及多梗死性痴呆患者血清S-100!NSE含量的测定.重庆医学,2004;33(6)803-804
24.Borusia kp,Herbold S.Serum neuron-specific enolase in children with febrile seizures:time profile and prognostic implications.BrainDev,2003;25:272-274
25.Oh SH,Lee JG;NA SJ,et al.The effect of initial serum neuron-specific Enolase level on clinical outcome in acute carotid artery territory infarction.Yonsei Med J,2002;43:357-362
26.Jordan W,Hasgedohm J,Wiltfang J,et al.Biochemical markres of cerebrovascular injury in sleep apnoea syndrome.Eur Respir J,2002;20:158-164
1.Donato R.S100:a multigenic family of calcium-modulated proteins of the EF-hand type with intracellular and extracellular tunctional roles.Int.J.Biochem.Cell Biol,2001;33:637-643
2.Michetti F,Gazzolo D.s100B protein in biological fluids:a tool for perinatal medicine(inpress).Clin Chem,2002;48:371
3.Fassbender k,Schmidt R,Schreiner A,et al.Leakage of brain-originated proteins in peripheral blood:temporal profile and diagnostic value in early ischemic Stroke.J Neurol Sci,1997;148:101-5
4.Buttner T,Weyers S,Postert T,et al.S-100 protein:serum marker of focal brain damage after ischemic territorial McA infarction.stroke,1997;28:1961-5
5.Abraha HD,Butterworth RJ,Bath PM,et al.serum S-100 protein relationship to clinical outcome in acute stroke.Ann Cline Biochem,1997;34:546-50
6.王兴河,秦梅,樊绍曾,等.大鼠缺氧缺血性脑损伤时血液和脑脊液中S-100、CK-BB、NSE、MBP水平变化的研究.中华儿科杂志,1999;37:670-672
7.陈惠珍,张培钦,曹岫岩.新生儿脑病S-100蛋白监测与预后的研究.中国妇幼保健,2003;18:40-42
8.Martens P,raabe A,Johnsson P.Serum S-100 and neuron-specific enolase for prediction of regaining consciousness after global cerebral ischemia.Stroke,1998;29:2363-2366
9.Kleindienst A,Harvey HB,Rice Ac,et al.Intraventricular infusion of the neurotrophic protein S100B improves cognitive recovery after fluid percussion injury in the rat.J Neurotrauma,2004;21:541-547
10.Ingebrigtsen T,Romner B.Biochemical serum markers for brain damage:a short review with emphasis on clinical utility in mild head injury.Rstor Neurol Neurosci,2003;21:171-176
11.Townend WJ,Guy MJ,Pani MA,et al.Head injury outcome prediction in the emergency department:a role for protein S-100b? J neurosurg Psychiatry,2002;73:542-546
12.Mussack T,Biberthaler P,Kanz KG,et al.Serum s-100 and interleukin -8 as predictive markers for comparative neurologic outcome analysis of patients after cardiac arrest and severe traumatic brain injury.crit Care Med,2002;30:2669-2674
13.赵钢,杨毅宁,粟秀初.中枢神经系统炎症患者脑脊液S-100B蛋白和神经元特异性烯醇化酶含量的测定.解放军医学杂志,2002;27:887-889
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15.Vos MJ,Postma TJ,Martens F,et al.Serum levels of S-100B protein and neuron-specific enolase in glioma patients:a pilot study Anticancer Res,2004;24:2511-2514
16.高东,王景周,向静.脑梗死及多梗死性痴呆患者血清S-100!NSE含量的测定.重庆医学,2004;33(6)803-804
17.Peskind ER,Griffin Ws,Akama Kt,et al.Cerebrospinal fluid S100B is elevated in the earlier stages of Alzheimers disease.Neurochem Int,2001 Nov-Dec;39(5-6):409-13
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21.Herrmann M,Jost S,Kutz S,et al.Temporal profile of release of neurobiochemical markers of brain damage after tr-aumatic brain injury is associaed with intracranial pathology as demonstrated in cranial computeized tomography.J Neurotrauma,2000;17(2):113-122
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23.朱凤莲,郭学鹏.CSFNSE评价新生儿缺氧缺血性脑病脑损伤程度.临床儿科杂志,1998;16(1):53
24.文志华,汪鹏.中枢神经系统感染患者血清NSE、SICAM-1的改变.微循环学杂杂志,2002;12(3)29-30
2.Hernnann M,Jort S,Kutz S,et al.Temporal profile of release of nenrobiochemical markers of brain damage after traumatic brain injury is associated with intraeranial pathology as demonstrated in cranial computerized tomography.J Neurotrauma,2000;17:113-122
3.Fassbender K,Schmidt,Schreiner A,et al.LeaKage of brain-originated proteins in peripheral blood:temporal profile and diagnostic value in early ischemic stroke.J Neurol Sci,1997;148:101-105
4.Wainwright MS,craft JM,Griffin WS,et al.Increased susceptibility of S-100B transgenic mice to perinatal hypoxia-ischemia.AnnNeurol,2004;56:61-67
5.汤慈美,王新德.神经病学.第7卷.北京:人民军医出版社,2001;342-343
6.ohen-Zion M,Stepnowsky C,Johnson s,et al.Cognitive changes and sleep disordered breathing in elderly:differences in race.JPsychosom Res,2004,56:549-553
7.Sateia MJ.Neuropsychological impairment and quality of life in obstructive sleep apnea.Clin Chest Med,2003;24:249-259
8.Engleman HM,Kingshott Rn,MartinSE,Douglas NJ.Congnitive function in the sleep apnea/hypopnea syndrome(SAHS).sleep,2000 Jun;15;23 supple 4:s 102-s108
9.Kingshott Rn,Engleman HM,Deary IJ,et al.Does arousal frequency predict daytime function ?Eur Respir J,1998;12:1264-1270
10.Findley Lt,Barth JT,PowersDC,et al.Cognitive impairments with obstructive sleep apnea and associated hypoxemia.chest,1986;90:686-690
11.Borak J,Cieslicki JK,Koziej M,et al.Effects of CPAP treatment on psychological status in patients with severe obstrctive sleep apnea.J sleep Res,1996;5:123-127
12.彭斌,李舜伟,黄席珍,等.睡眠呼吸暂停综合症及鼾症患者时间相关电位研究.中华医学杂志,2000;80:429-431
13.LindaJ,van Eldik,Mark S,et al.The janus face of glial-derived sl00B:Beneficialk and detrimental functions in the brain.restorative Neurology and neuroscience,2003;21:97-108
14.HerrmannM,VosP,WunderlichMT,etal.Release ofglial tissue-specific oroteins afte racute stroke:Acomparative analysis of serum concentrations of protein S-100Band glial fibrillary acidic protein.Stroke,2000;31:2670-2677
15.Palmio J,PeltolaJ,Vuorinen P,et al.Normal CSF neuron-specific enolase and S-100 protein levels in patients with recent non-complicated to nic-clonic seizures.J Neurol Sci,2001;183:27-31
16.Ploy MC,Chainier D,Tran-Thi NH,et al.Integron-asso-ciated antibiotic resistance in Salmonella enterica serovar type from Asia.Antimicrob Agents Chemother,2003;47:1427-1429
17.王淮燕,郭锡熔.窒息后缺氧缺血性新生儿脐血S-100B蛋白变化的意义.实用儿科临床杂志,2006;21:916-17
18.Hu J,Van Eldik LJ.S100B induces apoptotic cell death incultured astrocytes via a nitric oxide-dependent pathway.Biochem Biophy Acta,1996;1313:239-245
19.Gozal E,row BW,SchuA,et al.Developmental differences incorticaland hippocampal vulnerability to intermittent hypoxia in the rat,Neurosci.Lett.2001;305:197-201
20.Benowitz LI,RouttenbergA.a membrance phosphoprotein associated with neural development,axonal regeneration,phospholipids metabolkism,and synaptic plasticity.Trends Neurosci,1987;10:527-532
21.Holscher C.Nitric oxide,the enigmatic neuronal messengar:its role in synaptic plasticity.Trends in Neurosci,1997;20:298-303
22.Yamada K,Noda Y,Nakayama S,et al.Role of nitric oxide in learning and memory and in monoamine metabolism in the rat brain.Bri J Pharm,1995;115:852-858
23.高东,王景周,向静.脑梗死及多梗死性痴呆患者血清S-100!NSE含量的测定.重庆医学,2004;33(6)803-804
24.Borusia kp,Herbold S.Serum neuron-specific enolase in children with febrile seizures:time profile and prognostic implications.BrainDev,2003;25:272-274
25.Oh SH,Lee JG;NA SJ,et al.The effect of initial serum neuron-specific Enolase level on clinical outcome in acute carotid artery territory infarction.Yonsei Med J,2002;43:357-362
26.Jordan W,Hasgedohm J,Wiltfang J,et al.Biochemical markres of cerebrovascular injury in sleep apnoea syndrome.Eur Respir J,2002;20:158-164
1.Donato R.S100:a multigenic family of calcium-modulated proteins of the EF-hand type with intracellular and extracellular tunctional roles.Int.J.Biochem.Cell Biol,2001;33:637-643
2.Michetti F,Gazzolo D.s100B protein in biological fluids:a tool for perinatal medicine(inpress).Clin Chem,2002;48:371
3.Fassbender k,Schmidt R,Schreiner A,et al.Leakage of brain-originated proteins in peripheral blood:temporal profile and diagnostic value in early ischemic Stroke.J Neurol Sci,1997;148:101-5
4.Buttner T,Weyers S,Postert T,et al.S-100 protein:serum marker of focal brain damage after ischemic territorial McA infarction.stroke,1997;28:1961-5
5.Abraha HD,Butterworth RJ,Bath PM,et al.serum S-100 protein relationship to clinical outcome in acute stroke.Ann Cline Biochem,1997;34:546-50
6.王兴河,秦梅,樊绍曾,等.大鼠缺氧缺血性脑损伤时血液和脑脊液中S-100、CK-BB、NSE、MBP水平变化的研究.中华儿科杂志,1999;37:670-672
7.陈惠珍,张培钦,曹岫岩.新生儿脑病S-100蛋白监测与预后的研究.中国妇幼保健,2003;18:40-42
8.Martens P,raabe A,Johnsson P.Serum S-100 and neuron-specific enolase for prediction of regaining consciousness after global cerebral ischemia.Stroke,1998;29:2363-2366
9.Kleindienst A,Harvey HB,Rice Ac,et al.Intraventricular infusion of the neurotrophic protein S100B improves cognitive recovery after fluid percussion injury in the rat.J Neurotrauma,2004;21:541-547
10.Ingebrigtsen T,Romner B.Biochemical serum markers for brain damage:a short review with emphasis on clinical utility in mild head injury.Rstor Neurol Neurosci,2003;21:171-176
11.Townend WJ,Guy MJ,Pani MA,et al.Head injury outcome prediction in the emergency department:a role for protein S-100b? J neurosurg Psychiatry,2002;73:542-546
12.Mussack T,Biberthaler P,Kanz KG,et al.Serum s-100 and interleukin -8 as predictive markers for comparative neurologic outcome analysis of patients after cardiac arrest and severe traumatic brain injury.crit Care Med,2002;30:2669-2674
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