血清脑红蛋白评估新生儿低血糖脑损伤的临床价值
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摘要
目的探讨血清脑红蛋白(NGB)在新生儿低血糖脑损伤评估中的临床应用价值。方法选择100例低血糖新生儿为研究对象。根据振幅整合脑电图(aEEG)结果和/或临床表现,分为3组:症状性低血糖脑损伤组(n=22)、无症状性低血糖脑损伤组(n=37)和低血糖无脑损伤组(n=41)。比较各组患儿血糖、低血糖持续时间、NGB及神经元特异性烯醇化酶(NSE)水平、改良aEEG评分;分析NGB与NSE水平、改良aEEG评分之间的相关性并绘制受试者工作特征(ROC)曲线等。结果症状性低血糖脑损伤组血糖、改良aEEG评分低于无症状性低血糖脑损伤组及低血糖无脑损伤组(P<0.05),NGB、NSE、低血糖持续时间高/长于无症状性低血糖脑损伤组及低血糖无脑损伤组(P<0.05)。无症状低血糖脑损伤组血糖、改良aEEG评分低于低血糖无脑损伤组(P<0.05),NGB、NSE及低血糖持续时间高/长于低血糖无脑损伤组(P<0.05)。NGB与NSE、低血糖持续时间呈正相关(分别r=0.922、0.929,P<0.05),与血糖、改良aEEG评分呈负相关(分别r=-0.849、-0.968,P<0.05);NGB、NSE、改良a EEG评分的ROC曲线下面积分别为0.894、0.890、0.941,NGB最佳截断值为108mg/L,敏感度80.8%,特异度95.8%。结论血清NGB与NSE、改良aEEG评分比较,同样可作为评估低血糖新生儿脑损伤的特异性指标,具有一定的临床应用价值。[中国当代儿科杂志,2019,21(6):573-579]
Objective To study the clinical value of serum neuroglobin in evaluating hypoglycemic brain injury in neonates. Methods A total of 100 neonates with hypoglycemia were enrolled as subjects. According to amplitudeintegrated EEG(aEEG) findings and/or clinical manifestations, they were divided into symptomatic hypoglycemic brain injury group(n=22), asymptomatic hypoglycemic brain injury group(n=37) and hypoglycemic non-brain injury group(n=41). The three groups were compared in terms of blood glucose, duration of hypoglycemia, levels of neuroglobin and neuron-specific enolase(NSE), and modified aEEG score. The correlation of neuroglobin with NSE and modified aEEG score was analyzed. The receiver operating characteristic(ROC) curve was plotted. Results Compared with the asymptomatic hypoglycemic brain injury and hypoglycemic non-brain injury groups, the symptomatic hypoglycemic brain injury group had significantly lower blood glucose and modified aEEG score, significantly higher neuroglobin and NSE levels, and a significantly longer duration of hypoglycemia(P<0.05). Compared with the hypoglycemic non-brain injury group, the asymptomatic hypoglycemic brain injury group had significantly lower blood glucose and modified aEEG score, significantly higher neuroglobin and NSE levels, and a significantly longer duration of hypoglycemia(P<0.05). Neuroglobin was positively correlated with NSE and duration of hypoglycemia(r=0.922 and 0.929 respectively; P<0.05) and negatively correlated with blood glucose and modified aEEG score(r=-0.849 and-0.968 respectively; P<0.05). The areas under the ROC curve of neuroglobin, NSE and modified aEEG score were 0.894, 0.890 and 0.941 respectively, and neuroglobin had a sensitivity of 80.8% and a specificity of 95.8% at the optimal cut-off value of 108 mg/L. Conclusions Like NSE and modified aEEG score, serum neuroglobin can also be used as a specific indicator for the assessment of brain injury in neonates with hypoglycemia and has a certain value in clinical practice.[Chin J Contemp Pediatr, 2019, 21(6): 573-579]
Objective To study the clinical value of serum neuroglobin in evaluating hypoglycemic brain injury in neonates. Methods A total of 100 neonates with hypoglycemia were enrolled as subjects. According to amplitudeintegrated EEG(aEEG) findings and/or clinical manifestations, they were divided into symptomatic hypoglycemic brain injury group(n=22), asymptomatic hypoglycemic brain injury group(n=37) and hypoglycemic non-brain injury group(n=41). The three groups were compared in terms of blood glucose, duration of hypoglycemia, levels of neuroglobin and neuron-specific enolase(NSE), and modified aEEG score. The correlation of neuroglobin with NSE and modified aEEG score was analyzed. The receiver operating characteristic(ROC) curve was plotted. Results Compared with the asymptomatic hypoglycemic brain injury and hypoglycemic non-brain injury groups, the symptomatic hypoglycemic brain injury group had significantly lower blood glucose and modified aEEG score, significantly higher neuroglobin and NSE levels, and a significantly longer duration of hypoglycemia(P<0.05). Compared with the hypoglycemic non-brain injury group, the asymptomatic hypoglycemic brain injury group had significantly lower blood glucose and modified aEEG score, significantly higher neuroglobin and NSE levels, and a significantly longer duration of hypoglycemia(P<0.05). Neuroglobin was positively correlated with NSE and duration of hypoglycemia(r=0.922 and 0.929 respectively; P<0.05) and negatively correlated with blood glucose and modified aEEG score(r=-0.849 and-0.968 respectively; P<0.05). The areas under the ROC curve of neuroglobin, NSE and modified aEEG score were 0.894, 0.890 and 0.941 respectively, and neuroglobin had a sensitivity of 80.8% and a specificity of 95.8% at the optimal cut-off value of 108 mg/L. Conclusions Like NSE and modified aEEG score, serum neuroglobin can also be used as a specific indicator for the assessment of brain injury in neonates with hypoglycemia and has a certain value in clinical practice.[Chin J Contemp Pediatr, 2019, 21(6): 573-579]
引文
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[3]Zhang LN,Ai YH,Gong H,et al.Expression and role of neuroglobin in rats with sepsis-associated encephalopathy[J].Crit Care Med,2014,42(1):e12-e21.
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[8]徐文慧,刘娜娜,柳涛,等.改良aEEG、NCIS、SNAPPE-Ⅱ评分对高危儿脑损伤早期诊断价值比较[J].南昌大学学报(医学版),2015,55(2):25-31.
[9]刘晓燕,吴逊.临床脑电图学[M].北京:人民卫生出版社,2006:541-575.
[10]Stanley CA,Rozance PJ,Thornton PS,et al.Re-evaluating“transitional neonatal hypoglycemia”:mechanism and implications for management[J].J Pediar,2015,166(6):1520-1525.e1.
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[12]Boardman JP,Wusthoff CJ,Cowan FM.Hypoglycaemia and neonatal brain injury[J].Arch Dis Child Educ Pract Ed,2013,98(1):2-6.
[13]Jain A,Aggarwal R,Jeeva Sankar M,et al.Hypoglycemia in the newborn[J].Indian J Pediatr,2010,77(10):1137-1142.
[14]Harris DL,Weston PJ,Harding JE.Lactate,rather than ketones,may provide alternative cerebral fuel in hypoglycaemic newborns[J].Arch Dis Child Fetal Neonatal Ed,2015,100(2):F161-F164.
[15]顾秋芳,胡黎园,陈超,等.足月新生儿低血糖22例磁共振表现与临床特征[J].中国循证儿科杂志,2013,8(2):116-121.
[16]Arhan E,?ztürk Z,Serdaro?lu A,et al.Neonatal hypoglycemia:a wide range of electroclinical manifestations and seizure outcomes[J].Eur J Paediatr Neurol,2017,21(5):738-744.
[17]Styne DM,Arslanian SA,Connor EL,et al.Pediatric obesity-assessment,treatment and prevention:an Endocrine Society clinical practice guideline[J].J Clin Endotrinol Metab,2017,102(3):709-757.
[18]Wong DS,Poskitt KJ,Chau V,et al.Brain injury patterns in hypoglycemia in neonatal encephalopathy[J].AJNR Am JNeuroradiol,2013,34(7):1456-1461.
[19]Bonifacio SL,Glass HC,Peloquin S,et al.A new neurological focus in neonatal intensive care[J].Nat Rev Neurol,2011,7(9):485-494.
[20]郭志梅,刘芳,周春风,等.新生儿低血糖脑损伤振幅整合脑电图特征研究[J].临床儿科杂志,2013,31(11):1019-1023.
[21]程国强,施亿赟,邵肖梅,等.振幅整合脑电图评分系统评价新生儿脑发育的临床价值[J].中华围产医学杂志,2012,15(4):234-237.
[22]Brandner S,Thaler C,Buchfelder M,et al.Brain-derived protein concentrations in the cerebrospinal fluid:contribution of trauma resulting from ventricular drain insertion[J].J Neurotrauma,2013,30(13):1205-1210.
[23]Haque A,Polcyn R,Matzelle D,et al.New insights into the role of neuron-specific enolase in neuro-inflammation,neurodegeneration,and neuroprotection[J].Brain Sci,2018,8(2).pii:E33.
[24]李梅,刘长云,王永芹,等.新生儿低血糖血清NSE变化与头颅MRI相关性的临床研究[J].潍坊医学院学报,2010,32(6):417-419,422.
[25]臧丽娇,仇杰,庄根苗,等.血清S100B蛋白、神经元特异性烯醇化酶与新生儿低血糖脑损伤的相关性[J].山东大学学报(医学版),2016,54(4):51-54,59.
[26]Boron I,Capece L,Pennacchietti F,et al.Engineered chimeras reveal the structural basis of hexacoordination in globins:a case study of neuroglobin and myoglobin[J].Biochim Biophys Acta,2015,1850(1):169-177.
[27]Garofalo T,Ferri A,Sorice M,et al.Neuroglobin overexpression plays a pivotal role in neuroprotection through mitochondrial raft-like microdomains in neuroblastoma SK-N-BE2 cells[J].Mol Cell Neurosci,2018,88:167-176.
[28]张丽娜,胡森彬,邓松筠,等.DNA甲基化对细胞氧糖剥夺后复糖复氧模型中脑红蛋白持续表达的影响[J].中华医学杂志,2016,96(39):3164-3169.
[29]张莉,镇祥繁.新生儿低血糖及低血糖性脑损伤的研究进展[J].国际儿科学杂志,2013,40(5):477-480.
[30]林欣,李敏,胡亚卓,等.颅脑创伤后大鼠脑组织脑红蛋白表达变化及其与神经元凋亡的关系研究[J].中国应用生理学杂志,2010,26(1):39-44.
[31]Wakasugi K,Nakano T,Morishima I.Oxidized human neuroglobin acts as a heterotrimeric Gαprotein guanine nucleotide dissociation inhibitor[J].J Biol Chem,2003,278(38):36505-36512.
[2]Burmester T,Weich B,Reinhardt S,et al.A vertebrate globin expressed in the brain[J].Nature,2000,407(6803):520-523.
[3]Zhang LN,Ai YH,Gong H,et al.Expression and role of neuroglobin in rats with sepsis-associated encephalopathy[J].Crit Care Med,2014,42(1):e12-e21.
[4]赵璞.新生儿缺氧缺血性脑病血清NGB、CK-BB活力及NBNA评分的相关性分析[D].太原:山西医科大学,2011.
[5]施元美,张泓,周保健,等.新生儿缺氧缺血性脑病血清脑红蛋白水平与新生儿20项行为神经测定的相关性[J].蚌埠医学院学报,2013,38(11):1443-1445.
[6]邵肖梅,叶鸿瑁,丘小汕.实用新生儿学[M].第4版.北京:人民卫生出版社,2011:755.
[7]Burdjalov VF,Baumgart S,Spitzer AR.Cerebral function monitoring:a new scoring system for the evaluation of brain maturation in neonates[J].Pediatrics,2003,112(4):855-861.
[8]徐文慧,刘娜娜,柳涛,等.改良aEEG、NCIS、SNAPPE-Ⅱ评分对高危儿脑损伤早期诊断价值比较[J].南昌大学学报(医学版),2015,55(2):25-31.
[9]刘晓燕,吴逊.临床脑电图学[M].北京:人民卫生出版社,2006:541-575.
[10]Stanley CA,Rozance PJ,Thornton PS,et al.Re-evaluating“transitional neonatal hypoglycemia”:mechanism and implications for management[J].J Pediar,2015,166(6):1520-1525.e1.
[11]Harris DL,Weston PJ,Harding JE.Incidence of neonatal hypoglcemia in babies identified as at risk[J].J Pediatr,2012,161(5):787-791.
[12]Boardman JP,Wusthoff CJ,Cowan FM.Hypoglycaemia and neonatal brain injury[J].Arch Dis Child Educ Pract Ed,2013,98(1):2-6.
[13]Jain A,Aggarwal R,Jeeva Sankar M,et al.Hypoglycemia in the newborn[J].Indian J Pediatr,2010,77(10):1137-1142.
[14]Harris DL,Weston PJ,Harding JE.Lactate,rather than ketones,may provide alternative cerebral fuel in hypoglycaemic newborns[J].Arch Dis Child Fetal Neonatal Ed,2015,100(2):F161-F164.
[15]顾秋芳,胡黎园,陈超,等.足月新生儿低血糖22例磁共振表现与临床特征[J].中国循证儿科杂志,2013,8(2):116-121.
[16]Arhan E,?ztürk Z,Serdaro?lu A,et al.Neonatal hypoglycemia:a wide range of electroclinical manifestations and seizure outcomes[J].Eur J Paediatr Neurol,2017,21(5):738-744.
[17]Styne DM,Arslanian SA,Connor EL,et al.Pediatric obesity-assessment,treatment and prevention:an Endocrine Society clinical practice guideline[J].J Clin Endotrinol Metab,2017,102(3):709-757.
[18]Wong DS,Poskitt KJ,Chau V,et al.Brain injury patterns in hypoglycemia in neonatal encephalopathy[J].AJNR Am JNeuroradiol,2013,34(7):1456-1461.
[19]Bonifacio SL,Glass HC,Peloquin S,et al.A new neurological focus in neonatal intensive care[J].Nat Rev Neurol,2011,7(9):485-494.
[20]郭志梅,刘芳,周春风,等.新生儿低血糖脑损伤振幅整合脑电图特征研究[J].临床儿科杂志,2013,31(11):1019-1023.
[21]程国强,施亿赟,邵肖梅,等.振幅整合脑电图评分系统评价新生儿脑发育的临床价值[J].中华围产医学杂志,2012,15(4):234-237.
[22]Brandner S,Thaler C,Buchfelder M,et al.Brain-derived protein concentrations in the cerebrospinal fluid:contribution of trauma resulting from ventricular drain insertion[J].J Neurotrauma,2013,30(13):1205-1210.
[23]Haque A,Polcyn R,Matzelle D,et al.New insights into the role of neuron-specific enolase in neuro-inflammation,neurodegeneration,and neuroprotection[J].Brain Sci,2018,8(2).pii:E33.
[24]李梅,刘长云,王永芹,等.新生儿低血糖血清NSE变化与头颅MRI相关性的临床研究[J].潍坊医学院学报,2010,32(6):417-419,422.
[25]臧丽娇,仇杰,庄根苗,等.血清S100B蛋白、神经元特异性烯醇化酶与新生儿低血糖脑损伤的相关性[J].山东大学学报(医学版),2016,54(4):51-54,59.
[26]Boron I,Capece L,Pennacchietti F,et al.Engineered chimeras reveal the structural basis of hexacoordination in globins:a case study of neuroglobin and myoglobin[J].Biochim Biophys Acta,2015,1850(1):169-177.
[27]Garofalo T,Ferri A,Sorice M,et al.Neuroglobin overexpression plays a pivotal role in neuroprotection through mitochondrial raft-like microdomains in neuroblastoma SK-N-BE2 cells[J].Mol Cell Neurosci,2018,88:167-176.
[28]张丽娜,胡森彬,邓松筠,等.DNA甲基化对细胞氧糖剥夺后复糖复氧模型中脑红蛋白持续表达的影响[J].中华医学杂志,2016,96(39):3164-3169.
[29]张莉,镇祥繁.新生儿低血糖及低血糖性脑损伤的研究进展[J].国际儿科学杂志,2013,40(5):477-480.
[30]林欣,李敏,胡亚卓,等.颅脑创伤后大鼠脑组织脑红蛋白表达变化及其与神经元凋亡的关系研究[J].中国应用生理学杂志,2010,26(1):39-44.
[31]Wakasugi K,Nakano T,Morishima I.Oxidized human neuroglobin acts as a heterotrimeric Gαprotein guanine nucleotide dissociation inhibitor[J].J Biol Chem,2003,278(38):36505-36512.