阻塞性睡眠呼吸暂停伴认知障碍患者中血清miR-132表达及意义
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摘要
【目的】探讨miR-132在阻塞性睡眠呼吸暂停(OSA)伴认知障碍患者血清中的表达及其意义。【方法】根据蒙特利尔认知评估(MoCA)评分,将66名年龄在30～60岁之间的阻塞性睡眠呼吸暂停患者分为两组:认知障碍OSA组(OSAI组,n=36)、无认知障碍OSA组(OSAN组,n=30),30名无OSA的成年人作为对照组(HC组,n=30)。对其3组分别进行睡眠测试(OCST)和MoCA评估,并通过PCR检测血清中miR-132的相对表达量。【结果】HC组、OSAI组及OSAN组在年龄、教育程度、性别和高血压方面差异无统计学意义(P>0.05),与OSAN和HC组相比,OSAI组患者血清中miR-132的相对表达水平明显上调(P<0.001),并且与MoCA评分呈正相关(r=-0.726,P<0.001);ROC分析结果显示曲线下面积(AUC)具有统计学意义,具有认知功能障碍(AUC=0.935,95%CI:0.890-0.981,P<0.001)和OSA(AUC=0.787,95%CI:0.695-0.879,P<0.001)。【结论】血清miR-132表达水平升高与OSA的诊断及其认知功能障碍密切相关。血清miR-132的检测有可能成为OSA患者认知功能障碍及诊断的一个潜在指标。
【Objective】To explore the relationship between the miR-132 expression in serum and cognitive deficits of OSA.【Methods】 66 Chinese adults age 30 to 60 years old were enrolled and categorized into two groups based on Montreal Cognitive Assessment(MoCA)scores:OSA patients with cognitive impairment(OSAI,n=36),OSA patients without cognitive impairment(OSAN,n=30),and thirty adults without OSA as healthy control group(HC,n=30). Outof-center cardiopulmonary sleep testing(OCST)and MoCA assessment were performed and the relative expression of miR-132 in serum was detected by PCR.【Results】No significant difference was observed in age,education,gender and hypertension(P>0.05). The relative expression level of miR-132 was significantly up-regulated in OSAI patient′s serum compared to the OSAN and HC patients(P<0.001),and had a positive correlation with MoCA score(r=-0.726,P<0.001). ROC analyses showed that the areas under the curve(AUC)were statistically significant from the line of identity in OSA with cognitive impairment(AUC=0.935,95%CI:0.890-0.981,P<0.001)and in OSA(AUC=0.787,95%CI:0.695-0.879,P<0.001).【Conclusions】Elevated serum miR-132 expression levels are closely related to the diagnosis of OSA and its cognitive dysfunction. Detection of serum miR-132 may be a potential indicator of cognitive dysfunction and diagnosis in OSA patients.
【Objective】To explore the relationship between the miR-132 expression in serum and cognitive deficits of OSA.【Methods】 66 Chinese adults age 30 to 60 years old were enrolled and categorized into two groups based on Montreal Cognitive Assessment(MoCA)scores:OSA patients with cognitive impairment(OSAI,n=36),OSA patients without cognitive impairment(OSAN,n=30),and thirty adults without OSA as healthy control group(HC,n=30). Outof-center cardiopulmonary sleep testing(OCST)and MoCA assessment were performed and the relative expression of miR-132 in serum was detected by PCR.【Results】No significant difference was observed in age,education,gender and hypertension(P>0.05). The relative expression level of miR-132 was significantly up-regulated in OSAI patient′s serum compared to the OSAN and HC patients(P<0.001),and had a positive correlation with MoCA score(r=-0.726,P<0.001). ROC analyses showed that the areas under the curve(AUC)were statistically significant from the line of identity in OSA with cognitive impairment(AUC=0.935,95%CI:0.890-0.981,P<0.001)and in OSA(AUC=0.787,95%CI:0.695-0.879,P<0.001).【Conclusions】Elevated serum miR-132 expression levels are closely related to the diagnosis of OSA and its cognitive dysfunction. Detection of serum miR-132 may be a potential indicator of cognitive dysfunction and diagnosis in OSA patients.
引文
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[14]Kano M,Seki N,Kikkawa N,et al. miR-145,miR-133a and miR-133b:Tumor-suppressivemiRNAs target FSCN1 in esophageal squamous cellcarcinoma[J]. Int J Cancer,2010,127(12):2804-2814.
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[16]Hansen KF, Karelina K, Sakamoto K, et al.miRNA-132:a dynamic regulator of cognitivecapacity[J]. Brain Structure Function,2013,218(3):817-831.
[2] Xu M,Yang Y,Zhang J. Levels of neuroglobin inserum and neurocognitive impairments in Chinesepatients with obstructive sleep apnea[J]. SleepBreathing,2013,17(2):573-582.
[3] Vollono C,Testani E,Losurdo A,et al. Migraine,arousal and sleep deprivation:comment on:“sleepquality,arousal and pain thresholds in migraineurs:a blinded controlled polysomnographic study”[J]. JHeadache Pain,2013,14(1):50.
[4] Esposito M,Antinolfi L,Gallai B,et al. Executivedysfunction in children affected by obstructive sleepapnea syndrome:an observational study[J].Neuropsychiatr Dis Treat,2013,9:1087.
[5] Sales LV,Bruin VMSD,D′Almeida V,et al.Cognition and biomarkers of oxidative stress inobstructive sleep apnea[J]. Clinics,2013,68(4):449-455.
[6] Elad B,Lavie P. Effect of sleep apnea on cognitionand mood[J]. Int Rev Psychiatr,2005,17(4):277-282.
[7] An Z,Wang D,Yang G,et al. Role of microrna-130a in the pathogeneses of obstructive sleep apneahypopnea syndrome-associated pulmonaryhypertension by targeting the Gax gene[J].Medicine,2017,96(20).
[8] Huang S E,Zhao J,Huang D,et al. Serum miR-132 is a risk marker of post-stroke cognitiveimpairment[J]. Neurosci Lett,2016,615:102-106
[9] Ito E,Inoue Y. The International Classification ofSleep Disorders,third edition. American Academyof Sleep Medicine. Includes bibliographies and index[J]. Nihon Rinsho Jpn J Clin Med,2015,73(6):916.
[10]Horton DK,Hynan LS,Lacritz LH,et al. AnAbbreviated Montreal Cognitive Assessment(MoCA)for Dementia Screening[J]. ClinNeuropsychol,2015,29(4):413-425.
[11]Xu L,Han F,Keenan B T,et al. Validation of theNox-T3 Portable Monitor for Diagnosis ofObstructive Sleep Apnea in Chinese Adults[J]. JClin Sleep Med,2017,13(5):675.
[12]Chen C, Dong YH, Merchant R, et al. TheMontreal cognitive assessment(MoCA)is superiorto the mini-mental state examination(MMSE)indetecting patient′s with moderate cognitiveimpairment,no-dementia(CIND)and at high riskof dementia[J]. Alzheimers Dementia,2011,7(4):S240-S241.
[13]Shaltiel G,Hanan M,Wolf Y,et al. HippocampalmicroRNA-132 mediates stress-inducible cognitivedeficits through its acetylcholinesterase target[J].Brain Structure Function,2013,218(1):59-72.
[14]Kano M,Seki N,Kikkawa N,et al. miR-145,miR-133a and miR-133b:Tumor-suppressivemiRNAs target FSCN1 in esophageal squamous cellcarcinoma[J]. Int J Cancer,2010,127(12):2804-2814.
[15]Aten S,Hansen KF,Snider K,et al. miR-132couples the circadian clock to daily rhythms ofneuronal plasticity and cognition[J]. LearningMemory,2018,25(5):214-229.
[16]Hansen KF, Karelina K, Sakamoto K, et al.miRNA-132:a dynamic regulator of cognitivecapacity[J]. Brain Structure Function,2013,218(3):817-831.
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