脑出血疾病患者脑脊液中NSE、S100β及miR-124-3p、miR-146a-5p检测的临床意义
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摘要
目的探讨脑出血疾病患者脑脊液(CSF)中神经元特异性烯醇化酶(NSE)、酸性钙结合蛋白(S100β)及差异表达的miRNA在疾病诊断与病情评估中的价值。方法选择脑出血(ICH)疾病患者26例,依据格拉斯哥评分(GCS)将其分为轻度ICH组(13例)、重度ICH组(13例),并选取22例同期排除脑部疾病住院病人作为对照,采用实时荧光定量PCR检测所有入组对象CSF样本中的15个靶标微小RNA(miRNA),同时采用生化及化学发光方法检测β2微球蛋白(β2-MG)、天门冬氨酸氨基转移酶(AST)、乳酸(LAC)、乳酸脱氢酶(LD)、微量清蛋白(mAlb)、NSE、S100β,统计分析上述指标在诊断脑出血的效能及评估病情中的价值。结果轻度ICH组CSF NSE:17.48(8.64,26.86)ng/mL,S100β:1.40(0.38,2.11)μg/L,重度ICH组CSF NSE:18.55(8.86,24.69)ng/mL,S100β:1.51(1.10,4.64)μg/L,明显高于对照组[NSE:2.93(2.48,3.83)ng/mL,S100β:0.43(0.25,0.88)μg/L],差异有统计学意义(P<0.05);ICH患者CSF NSE的水平与出血量显著相关(r=0.86;P<0.01);与对照组比较,ICH组CSF miR-124-3p和miR-146a-5p显著上调,差异有统计学意义(P<0.05)。CSF中NSE、S100β、miR-124-3p、miR-146a-5p诊断ICH的曲线下面积(AUC)分别为0.931[95%置信区间(95%CI):0.857～0.892]、0.795(95%CI:0.670～0.921)、0.667(95%CI:0.512～0.822)和0.878(95%CI:0.776～0.844)。CSF中NSE、S100β两者联合诊断ICH的AUC为0.945,灵敏度为84.6%,特异度为98.2%。结论 CSF中NSE、S100β、miR-124-3p、miR-146a-5p的检测对于ICH的辅助诊断具有一定价值,尤其NSE、S100β可反映脑组织损伤严重程度。
Objective To investigate the value of neuron-specific enolase(NSE),acidic calcium-binding protein(S100β)and differentially expressed miRNA in cerebrospinal fluid(CSF)in patients with cerebral hemorrhage disease in disease diagnosis and disease assessment.Methods 26 patients with cerebral hemorrhage(ICH)disease were enrolled and divided into mild ICH group(13 cases)and severe ICH group(13 cases)according to Glasgow score(GCS).22 patients who were excluded from brain diseases in the same period were selected as the control group.Biochemical and chemiluminescence methods were used to detectβ2 microglobulin(β2-MG),aspartate aminotransferase(AST),lactic acid(LAC),lactate dehydrogenase(LD),microalbumin(mAlb),NSE,S100β.The efficacy of the above indicators in the diagnosis of cerebral hemorrhage and the value in the assessment of the condition were analyzed.Results CSF NSE in the mild ICH group was17.48(8.64,26.86)ng/mL,S100βwas 1.40(0.38,2.11)μg/L.CSF NSE in severe ICH group was 18.55(8.86,24.69)ng/mL,S100βwas 1.51(1.10,4.64)ug/L,which were significantly higher than those in the control group[NSE:2.93(2.48,3.83)ng/mL,S100β:0.43(0.25,0.88)μg/L],and the differences were statistically significant(P<0.05);The level of CSF NSE in patients with ICH was significantly correlated with the amount of bleeding(r=0.86,P<0.01).Compared with the control group,CSF miR-124-3 p and miR-146 a-5 p were significantly up-regulated in the ICH group,and the differences were statistically significant(P<0.05).The area under curve(AUC)of ICH in NSE,S100β,miR-124-3 p,and miR-146 a-5 p in CSF were0.931[95%confidence interval(95%CI):0.857-0.892],0.795(95%CI:0.670-0.921),0.667(95%CI:0.512-0.822)and 0.878(95%CI:0.776-0.844).The AUC of combined diagnosis of NSE and S100βin CSF for ICH was 0.945,the sensitivity was 84.6%,and the specificity was 98.2%.Conclusion The detection of NSE,S100β,miR-124-3 p and miR-146 a-5 p in CSF has certain value for the auxiliary diagnosis of ICH,especially NSE and S100βcan reflect the severity of brain tissue damage.
Objective To investigate the value of neuron-specific enolase(NSE),acidic calcium-binding protein(S100β)and differentially expressed miRNA in cerebrospinal fluid(CSF)in patients with cerebral hemorrhage disease in disease diagnosis and disease assessment.Methods 26 patients with cerebral hemorrhage(ICH)disease were enrolled and divided into mild ICH group(13 cases)and severe ICH group(13 cases)according to Glasgow score(GCS).22 patients who were excluded from brain diseases in the same period were selected as the control group.Biochemical and chemiluminescence methods were used to detectβ2 microglobulin(β2-MG),aspartate aminotransferase(AST),lactic acid(LAC),lactate dehydrogenase(LD),microalbumin(mAlb),NSE,S100β.The efficacy of the above indicators in the diagnosis of cerebral hemorrhage and the value in the assessment of the condition were analyzed.Results CSF NSE in the mild ICH group was17.48(8.64,26.86)ng/mL,S100βwas 1.40(0.38,2.11)μg/L.CSF NSE in severe ICH group was 18.55(8.86,24.69)ng/mL,S100βwas 1.51(1.10,4.64)ug/L,which were significantly higher than those in the control group[NSE:2.93(2.48,3.83)ng/mL,S100β:0.43(0.25,0.88)μg/L],and the differences were statistically significant(P<0.05);The level of CSF NSE in patients with ICH was significantly correlated with the amount of bleeding(r=0.86,P<0.01).Compared with the control group,CSF miR-124-3 p and miR-146 a-5 p were significantly up-regulated in the ICH group,and the differences were statistically significant(P<0.05).The area under curve(AUC)of ICH in NSE,S100β,miR-124-3 p,and miR-146 a-5 p in CSF were0.931[95%confidence interval(95%CI):0.857-0.892],0.795(95%CI:0.670-0.921),0.667(95%CI:0.512-0.822)and 0.878(95%CI:0.776-0.844).The AUC of combined diagnosis of NSE and S100βin CSF for ICH was 0.945,the sensitivity was 84.6%,and the specificity was 98.2%.Conclusion The detection of NSE,S100β,miR-124-3 p and miR-146 a-5 p in CSF has certain value for the auxiliary diagnosis of ICH,especially NSE and S100βcan reflect the severity of brain tissue damage.
引文
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[8]张极星,张艳国,赵亮,等.急性期脑出血患者血清ICAM-1,MMP-9,TNF-α,IL-6水平和出血灶周围水肿脑组织体积的相关性[J].山东医药,2017,57(27):58-60.
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[13]XU L,LINA W,XUEJUN Y.The diagnostic value of serum CEA,NSE and MMP-9for on-small cell lung cancer[J].Open Med(Wars),2016,11(1):59-62.
[14]CASMIRO M,MAITAN S,DE PASQUALE F,et al.Cerebrospinal fluid and serum neuron-specific enolase concentrations in a normal population[J].Eur J Neurol,2005,12(5):369-374.
[15]MORITZ S,WARNAT J,BELE S,et al.The prognostic value of NSE and S100Bfrom serum and cerebrospinal fluid in patients with spontaneous subarachnoid hemorrhage[J].J Neurosurg Anesthesiol,2010,22(1):21-31.
[16]齐英斌,许卓,李丽,等.急性脑梗死患者血清中NSE与S-100β蛋白的表达情况及其与脑损伤严重程度的相关性[J].中国实验诊断学,2015,18(12):2024-2026.
[17]STOICEA N,DU A,LAKIS D C,et al.The MiRNA journey from theory to practice as a CNS biomarker[J].Front Genet,2016,7(82):11.
[18]IWUCHUKWU I,NGUYEN D,SULAIMAN W.MicroRNA profile in cerebrospinal fluid and plasma of patients with spontaneous intracerebral hemorrhage[J].CNS Neurosci Ther,2016,22(12):1015-1018.
[19]CHAUDHRY S R,STOFFEL-WAGNER B,KINFE TM,et al.Elevated systemic IL-6levels in patients with aneurysmal subarachnoid hemorrhage is an unspecific marker for Post-SAH complications[J].Int J Mol Sci,2017,18(12):2580.
[20]GENG L J,LIU W,CHEN Y.miR-124-3p attenuates MPP+-induced neuronal injury by targeting STAT3in SH-SY5Ycells[J].Exp Biol Med,2017,242(18):1757-1764.
[21]ZHU Y,WANG J L,HE Z Y,et al.Association of altered serum MicroRNAs with perihematomal edema after acute intracerebral hemorrhage[J].PLoS One,2015,10(7):e0133783.
[2]ZHENG H W,WANG Y L,LIN J X,et al.Circulating MicroRNAs as potential risk biomarkers for hematoma enlargement after intracerebral hemorrhage[J].CNS Neurosci Ther,2012,18(12):1003-1011.
[3]FENG W,FENG Y.MicroRNAs in neural cell development and brain diseases[J].Sci China Life Sci,2011,54(12):1103-1112.
[4]GATLI G,ANIK A,ACAR S,et al.Brain injury markers:S100calcium-binding protein B,neuron-specific enolase and glial fibrillary acidic protein in children with diabetic ketoacidosis[J].Pediatr Diabetes,2018,19(5):1000-1006.
[5]HAJDUKOVA L,SOBEK O,PRCHALOVA D,et al.Biomarkers of brain damage:S100Band NSE concentrations in cerebrospinal Fluid-A normative study[J].Biomed Res Int,2015,89(12):379071.
[6]YANG T,GU J W,KONG B,et al.Gene expression profiles of patients with cerebral hematoma following spontaneous intracerebral hemorrhage[J].Mol Med Rep,2014,10(4):1671-1678.
[7]李武英,金俊,陈健,等.脑梗死和脑出血患者外周血中循环microRNA表达谱差异的初步分析[J].实用医学杂志,2014,30(11):1750-1753.
[8]张极星,张艳国,赵亮,等.急性期脑出血患者血清ICAM-1,MMP-9,TNF-α,IL-6水平和出血灶周围水肿脑组织体积的相关性[J].山东医药,2017,57(27):58-60.
[9]POWERS C J,DICKERSON R,ZHANG S W,et al.Human cerebrospinal fluid microRNA:temporal changes following subarachnoid hemorrhage[J].Physiol Genomics,2016,48(5):361-366.
[10]KIISKI H,LNGSJJ,TENHUNEN J,et al.S100B,NSE and MMP-9fail to predict neurologic outcome while elevated S100Bassociates with milder initial clinical presentation after aneurysmal subarachnoid hemorrhage[J].JNeurol Sci,2018,390(2):129-134.
[11]王广斌,季泰令.S100B蛋白、NSE作为脑损伤标志物的研究进展[J].中国老年学杂志,2011,31(5):890-892.
[12]GONZALEZ-GARCIA S,GONZALEZ-QUEVEDO A,FERNANDEZ-CONCEPCIN O,et al.Short-term prognostic value of serum neuron specific enolase and S100Bin acute stroke patients[J].Clin Biochem,2012,45(16/17):1302-1307.
[13]XU L,LINA W,XUEJUN Y.The diagnostic value of serum CEA,NSE and MMP-9for on-small cell lung cancer[J].Open Med(Wars),2016,11(1):59-62.
[14]CASMIRO M,MAITAN S,DE PASQUALE F,et al.Cerebrospinal fluid and serum neuron-specific enolase concentrations in a normal population[J].Eur J Neurol,2005,12(5):369-374.
[15]MORITZ S,WARNAT J,BELE S,et al.The prognostic value of NSE and S100Bfrom serum and cerebrospinal fluid in patients with spontaneous subarachnoid hemorrhage[J].J Neurosurg Anesthesiol,2010,22(1):21-31.
[16]齐英斌,许卓,李丽,等.急性脑梗死患者血清中NSE与S-100β蛋白的表达情况及其与脑损伤严重程度的相关性[J].中国实验诊断学,2015,18(12):2024-2026.
[17]STOICEA N,DU A,LAKIS D C,et al.The MiRNA journey from theory to practice as a CNS biomarker[J].Front Genet,2016,7(82):11.
[18]IWUCHUKWU I,NGUYEN D,SULAIMAN W.MicroRNA profile in cerebrospinal fluid and plasma of patients with spontaneous intracerebral hemorrhage[J].CNS Neurosci Ther,2016,22(12):1015-1018.
[19]CHAUDHRY S R,STOFFEL-WAGNER B,KINFE TM,et al.Elevated systemic IL-6levels in patients with aneurysmal subarachnoid hemorrhage is an unspecific marker for Post-SAH complications[J].Int J Mol Sci,2017,18(12):2580.
[20]GENG L J,LIU W,CHEN Y.miR-124-3p attenuates MPP+-induced neuronal injury by targeting STAT3in SH-SY5Ycells[J].Exp Biol Med,2017,242(18):1757-1764.
[21]ZHU Y,WANG J L,HE Z Y,et al.Association of altered serum MicroRNAs with perihematomal edema after acute intracerebral hemorrhage[J].PLoS One,2015,10(7):e0133783.