血浆IL-17A与脑白质病变及血管性认知障碍的相关性研究
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摘要
目的探讨血浆IL-17A水平与脑白质病变及血管性认知障碍(VCI)的相关性。方法选取有脑血管病危险因素或脑血管疾病患者,根据VCI诊断标准分为正常对照组(NCI组,n=82)和血管性认知障碍组(VCI组,n=96),分别应用酶联免疫吸附试验(ELISA)法测定2组患者血浆IL-17A浓度;使用蒙特利尔认知评估量表(MoCA)评定入组患者的认知功能;采用改良版本Scheltens量表对入组患者头颅MRI检查提示的脑白质病变进行评分。结果 NCI组和VCI组血浆IL-17A浓度分别为(22.65±5.20)ng/mL和(33.79±7.69)ng/mL,差异有统计学意义(P<0.05);NCI组和VCI组改良Scheltens量表评分分别为(3.76±3.32)分和(11.94±6.83)分,差异有统计学意义(P<0.05);对VCI组患者MoCA评分、血清IL-17A浓度、改良Scheltens量表评分进行两两Pearson相关性分析显示,MoCA评分与血浆IL-17A浓度呈负相关(r=-0.759,P<0.01),MoCA评分与改良Scheltens量表评分呈负相关(r=-0.893,P<0.01),血浆IL-17A浓度与改良Scheltens量表评分呈正相关(r=0.851,P<0.01)。结论血浆IL-17A可能作为判断脑白质病变严重程度及VCI患者认知功能损害程度的生物学指标。
Objective To explore the relationship between serum interleukin 17 A(IL-17 A) and white matter lesion and vascular cognitive impairment(VCI).Methods Patients with cerebrovascular diseases or cerebrovascular risk factors were selected and divided into two groups according to VCI diagnostic criteria:normal control group(NCI group,n=82),and vascular cognitive impairment group(VCI group,n=96).The concentration of serum IL-17 A was determined by enzyme-linked immunosorbent assay(ELISA).Montreal cognitive assessment(MoCA)were used to evaluate the cognitive function.The modified Scheltens were used to assess the severity of white matter lesions(WML).Results The serum levels of IL-17 A in NCI and VCI groups was(22.65±5.20) ng/mL and(33.79±7.69) ng/mL,respectively,which was statistically significant(P<0.05).The correlation analysis revealed that the serum IL-17 A levels were negatively correlated with the total MoCA scores(r=-0.759,P<0.01).The modified Scheltens scores were positively correlated with the total MoCA scores(r=-0.893,P<0.01),and the serum IL-17 A levels were negatively correlated with the modified Scheltens scores(r=0.851,P<0.01)in VCI group.Conclusion The concentration of serum IL-17 A was related to white matter lesion and cognitive impairment in patients with VCI.
Objective To explore the relationship between serum interleukin 17 A(IL-17 A) and white matter lesion and vascular cognitive impairment(VCI).Methods Patients with cerebrovascular diseases or cerebrovascular risk factors were selected and divided into two groups according to VCI diagnostic criteria:normal control group(NCI group,n=82),and vascular cognitive impairment group(VCI group,n=96).The concentration of serum IL-17 A was determined by enzyme-linked immunosorbent assay(ELISA).Montreal cognitive assessment(MoCA)were used to evaluate the cognitive function.The modified Scheltens were used to assess the severity of white matter lesions(WML).Results The serum levels of IL-17 A in NCI and VCI groups was(22.65±5.20) ng/mL and(33.79±7.69) ng/mL,respectively,which was statistically significant(P<0.05).The correlation analysis revealed that the serum IL-17 A levels were negatively correlated with the total MoCA scores(r=-0.759,P<0.01).The modified Scheltens scores were positively correlated with the total MoCA scores(r=-0.893,P<0.01),and the serum IL-17 A levels were negatively correlated with the modified Scheltens scores(r=0.851,P<0.01)in VCI group.Conclusion The concentration of serum IL-17 A was related to white matter lesion and cognitive impairment in patients with VCI.
引文
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[19] CHANG S H,DONG C.A novel heterodimeric cyto-kine consisting of IL-17 and IL-17F regulates inflammatory responses[J].Cell Res,2007,17(5):435-440.
[20] GELDERBLOM M,WEYMAR A,BERNREUTHER C,et al.Neutralization of the IL-17 axis diminishes neutrophil invasion and protects from ischemic stroke[J].Blood,2012,120:3 793-3 802.
[21] WAISMAN A,HAUPTMANN J,REGEN T.The role of IL-17 in CNS diseases[J].Acta Neuropathol,2015,129:625-637.
[22] TIAN A,MA H,CAO X,et al.Vitamin D Improves cognitive Function and Modulates Th17/Treg Cell Balance After Hepatectomy in Mice[J].Inflammation,2015,38(2):500-509.DOI:10.1007/s10753-014-9956-4.
[23] TULADHAR A M,VAN NORDEN A G,DE LAAT K F.White matter integrity in small vessel disease is related to cognition[J].Neuroimage Clin,2015,7:518-524.
[24] HATTORI Y,ENMI J,KITAMURA A,et al. A novel mouse model of subcortical infarcts with dementia[J].J Neurosci,2015,35(9):3 915-3 928.
[25] SON S J,LEE K S,LEE Y,et al.Association between white matter hyperintensity severity and cognitive impairment according to the presence of the apolipopro-tein E (APOE) ε4 allele in the elderly:retrospective analysis of data from the CREDOS study[J].J Clin Psychiatry,2012,73(12):1 555-1 562.DOI:10.4088/JCP.12m07702.
[26] PRASAD K,WIRYASAPUTRA L,NG A,et al.White matter disease independently predicts progression from mild cognitive impairment to Alzheimer's disease in a clinic cohort[J].Dement Geriatr Cogn Disord,2011,31(6):431-434.DOI:10.1159/000330019.
[27] HE S,LI L,HU J,et al.Effectiveness of Traditional Chinese Medicine (TCM) treatments on the cognitive functioning of elderly persons with mild cognitive impairment associated with white matter lesions[J].Shanghai Arch Psychiatry,2015,27(5):289-295.DOI:10.11919/j.issn.1002-0829.215109.
[28] YAN T,YU J R,ZHANG Y P,et al.Analysis on correlation of white matter lesion and lacunar infarction with vascular cognitive impairment[J].Int J Clin Exp Med,2015,8(8):14 119-14 122.
[29] Silbert L C,Dodge H H,Perkins L G,et al.Trajectory of white matter hyperintensity burden preceding mild cognitive impairment[J].Neurology,2012,79(8):741-747.
[30] CONSTANTINESCU C,TANI M,RANSOHOFF R,et al.Astrocytes as antigen-presenting cells:expression of IL-12 / IL-23[J].J Neurochem,2005,95:331-340.
[2] 国家卫计委脑卒中防治工程委员会.中国血管性认知障碍诊疗指导规范(2016)[J].全科医学临床与教育,2016,14(5):484-487.
[3] HARRISON S L,TANG E Y,KEAGE H A,et al.A Systematic Review of the Definitions of Vascular Cognitive Impairment,No Dementia in Cohort Studies[J].Dement Geriatr Cogn Disord,2016,42(1/2):69-79.DOI:10.1159/000448213.
[4] ZAMBONI G,GRIFFANTI L,JENKINSON M,et al.White Matter Imaging Correlates of Early Cognitive Impairment Detected by the Montreal Cognitive Assessment After Transient Ischemic Attack and Minor Stroke[J].Stroke,2017,48(6):1 539-1 547.DOI:10.1161/STROKEAHA.116.016044.
[5] BROOKES R L,HOLLOCKS M J,TAN R Y,et al.Brief Screening of Vascular Cognitive Impairment in Patients With Cerebral Autosomal-Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy Without Dementia[J].Stroke,2016,47(10):2 482-2 487.DOI:10.1161/STROKEAHA.116.013761.
[6] KAMAKURA C K,UENO Y,SAKAI Y,et al.White matter lesions and cognitive impairment may be related to recovery from unilateral spatial neglect after stroke[J].J Neurol Sci,2017,379:241-246.DOI:10.1016/j.jns.2017.06.021.
[7] SIVAKUMAR L,RIAZ P,KATE M,et al.White matter hyperintensity volume predicts persistent cognitive impairment in transient ischemic attack and minor stroke[J].Int J Stroke,2017,12(3):264-272.DOI:10.1177/1747493016676612.
[8] MOK V,WONG K K,XIONG Y,et al.Cortical and frontal atrophy are associated with cognitive impairment in age-related confluent white-matter lesion[J].J Neurol Neurosurg Psychiatry,2011,82(1):52-57.DOI:10.1136/jnnp.2009.201665.
[9] MALIN W,SARA H,KATARINA N,et al.Cerebro-spinal fluid levels of IL-6 are decreased and correlate with cognitive status in DLB patients[J].Alzheimers Res Ther,2015,7(5):63.
[10] MONTES M,ZHANG X,BERTHELOT L,et al.Oligoclonal myelin-reactive T-cell infiltrates derived from multiple sclerosis lesions are enriched in Th17 cells[J].Clin Immunol,2009,130(2):133-144.DOI:10.1016/j.clim.2008.08.030.
[11] GUOPING P,WEI W,XIAOYAN L,et al.Characteristics of the peripheral T cell immune response of patients at different stages of vascular cognitive impairment[J].Immunol Lett,2015,168(1):120-125.DOI:10.1016/j.imlet.2015.09.015.
[12] COHEN R A,ALEXANDER G E.Using the Telephone Interview for Cognitive Status and Telephone Montreal Cognitive Assessment for Evaluating Vascular Cognitive Impairment:Promising Call or Put on Hold?[J].Stroke,2017,48(11):2 919-2 921.doi:10.1161/STROKEAHA.117.018828.
[13] ZUO L,DONG Y,ZHU R,et al.Screening for cognitive impairment with the Montreal Cognitive Assessment in Chinese patients with acute mild stroke and transient ischaemic attack:a validation study[J].BMJ Open,2016,6(7):e011310.DOI:10.1136/bmjopen-2016-011310.
[14] DONG Y,XU J,CHAN B P,et al.The Montreal Cognitive Assessment is superior to National Institute of Neurological Disease and Stroke-Canadian Stroke Network 5-minute protocol in predicting vascular cognitive impairment at 1 year[J].BMC Neurol,2016,16:46.DOI:10.1186/s12883-016-0570-y.
[15] ZHANG L,DONG W,HAN J,et al.Montreal cognitive assessment and analysis of related factors for cognitive impairment in patients with chronic cerebral circulation insufficiency[J].Int J Psychiatry Med,2015,50(3):257-270.DOI:10.1177/0091217415610306.
[16] ?ARAC H,MARKELJEVIC J,ERDELJIC V,et al.Signal hyperintensities on brain magnetic resonance imaging in patients with primary Sj?gren syndrome and frequent episodic tension-type headache:relation to platelet serotonin level and disease activity[J].J Neurol Sci,1993,114(8):7-12.
[17] MARSHALL R S,FESTA J R,CHEUNG Y K,et al.Cerebral hemodynamics and cognitive impairment:baseline data from the RECON trial[J].Neurology,2012,78:250-255.
[18] 吴纪霞,庄雷,刘洁一,等.缺血性血管性认知障碍与血浆生化预测指标的探讨[J].中国实用神经疾病杂志,2018,21(2):188-192.
[19] CHANG S H,DONG C.A novel heterodimeric cyto-kine consisting of IL-17 and IL-17F regulates inflammatory responses[J].Cell Res,2007,17(5):435-440.
[20] GELDERBLOM M,WEYMAR A,BERNREUTHER C,et al.Neutralization of the IL-17 axis diminishes neutrophil invasion and protects from ischemic stroke[J].Blood,2012,120:3 793-3 802.
[21] WAISMAN A,HAUPTMANN J,REGEN T.The role of IL-17 in CNS diseases[J].Acta Neuropathol,2015,129:625-637.
[22] TIAN A,MA H,CAO X,et al.Vitamin D Improves cognitive Function and Modulates Th17/Treg Cell Balance After Hepatectomy in Mice[J].Inflammation,2015,38(2):500-509.DOI:10.1007/s10753-014-9956-4.
[23] TULADHAR A M,VAN NORDEN A G,DE LAAT K F.White matter integrity in small vessel disease is related to cognition[J].Neuroimage Clin,2015,7:518-524.
[24] HATTORI Y,ENMI J,KITAMURA A,et al. A novel mouse model of subcortical infarcts with dementia[J].J Neurosci,2015,35(9):3 915-3 928.
[25] SON S J,LEE K S,LEE Y,et al.Association between white matter hyperintensity severity and cognitive impairment according to the presence of the apolipopro-tein E (APOE) ε4 allele in the elderly:retrospective analysis of data from the CREDOS study[J].J Clin Psychiatry,2012,73(12):1 555-1 562.DOI:10.4088/JCP.12m07702.
[26] PRASAD K,WIRYASAPUTRA L,NG A,et al.White matter disease independently predicts progression from mild cognitive impairment to Alzheimer's disease in a clinic cohort[J].Dement Geriatr Cogn Disord,2011,31(6):431-434.DOI:10.1159/000330019.
[27] HE S,LI L,HU J,et al.Effectiveness of Traditional Chinese Medicine (TCM) treatments on the cognitive functioning of elderly persons with mild cognitive impairment associated with white matter lesions[J].Shanghai Arch Psychiatry,2015,27(5):289-295.DOI:10.11919/j.issn.1002-0829.215109.
[28] YAN T,YU J R,ZHANG Y P,et al.Analysis on correlation of white matter lesion and lacunar infarction with vascular cognitive impairment[J].Int J Clin Exp Med,2015,8(8):14 119-14 122.
[29] Silbert L C,Dodge H H,Perkins L G,et al.Trajectory of white matter hyperintensity burden preceding mild cognitive impairment[J].Neurology,2012,79(8):741-747.
[30] CONSTANTINESCU C,TANI M,RANSOHOFF R,et al.Astrocytes as antigen-presenting cells:expression of IL-12 / IL-23[J].J Neurochem,2005,95:331-340.