亚低温治疗对缺氧缺血性脑病新生儿血清神经胶质酸性蛋白和泛素羧基末端水解酶L1的影响

蒋曙红; 王金秀; 张一鸣; 蒋惠芬

doi:10.7499/j.issn.1008-8830.2014.12.001

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中国当代儿科杂志 ›› 2014, Vol. 16 ›› Issue (12) : 1193-1196. DOI: 10.7499/j.issn.1008-8830.2014.12.001

论著·临床研究

亚低温治疗对缺氧缺血性脑病新生儿血清神经胶质酸性蛋白和泛素羧基末端水解酶L1的影响

蒋曙红, 王金秀, 张一鸣, 蒋惠芬

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Effect of hypothermia therapy on serum GFAP and UCH-L1 levels in neonates with hypoxic-ischemic encephalopathy

JIANG Shu-Hong, WANG Jin-Xiu, ZHANG Yi-Ming, JIANG Hui-Fen

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摘要

目的研究缺氧缺血性脑病(HIE)新生儿亚低温治疗后血清神经胶质酸性蛋白(GFAP)和泛素羧基末端水解酶L1(UCH-L1)的表达水平并探讨其价值.方法选取64例HIE新生儿,其中33例轻度患儿采取一般治疗,31例中、重度患儿给予一般治疗和亚低温治疗,采用ELISA检测患儿治疗前和治疗后(6~12 h)血清GFAP和UCH-L1的水平.结果治疗前中、重度HIE组患儿血IL-6、IL-8、GFAP以及UCH-L1水平高于轻度HIE组(P<0.01).相关性分析显示血GFAP水平与IL-6、IL-8呈正相关(分别r=0.54、0.63,P<0.05),与Apgar评分呈负相关(r=-0.47,P<0.05).治疗后,中、重度组患儿血IL-6、IL-8、UCH-L1水平低于治疗前(P<0.05),但GFAP水平高于治疗前(P<0.01).生后15~18个月后的随访发现神经发育不良的患儿血GFAP水平高于预后良好的患儿(P<0.01).ROC曲线显示GFAP和UCH-L1的诊断曲线下面积为0.714和0.703;当GFAP的诊断阈值为0.07 ng/mL时,其诊断的敏感性为77%,特异性为78%.结论亚低温治疗可致HIE患儿血清UCH-L1水平降低,GFAP水平升高;血清GFAP、UCH-L1水平可反映HIE患儿治疗前后脑细胞的变化,有望成为新的HIE的血清学辅助诊断指标.

Abstract

Objective To evaluate the effect of hypothermia therapy on serum glial fibrillary acidic protein (GFAP) and ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1) levels in neonates with hypoxic-ischemic encephalopathy (HIE). Methods Sixty-four HIE neonates were enrolled in this study. Thirty-three neonates with mild HIE were given conventional treatment and 31 neonates with moderate or severe HIE received conventional treatment and hypothermia therapy. Serum levels of GFAP and UCH-L1 were measured using ELISA before treatment and 6-12 hours after treatment. Results Serum levels of IL-6, IL-8, GFAP and UCH-L1 in the moderate/severe HIE group were significantly higher than in the mild HIE group (P<0.05) before treatment. Serum GFAP level was positively correlated with serum IL-6 (r=0.54; P<0.05) and IL-8 levels (r=0.63; P<0.05) , while negatively correlated with Apgar score (r=-0.47, P<0.05). After treatment, serum levels of IL-6, IL-8 and UCH-L1 in the moderate/severe HIE group were significantly reduced (P<0.05), while serum GFAP levels increased significantly (P<0.05). The patients with abnormal neurological development showed higher serum GFAP levels than those with favourable prognosis (P<0.05). Receiver operating characteristic (ROC) curves analysis demonstrated that the area under curve (AUC) of GFAP and UCH-L1 were 0.714 and 0.703 respectively. At a cut-off value of 0.07 ng/mL, the sensitivity and specificity of GFAP for the diagnosis of HIE were 77% and 78% respectively. Conclusions Hypothermia therapy can decrease serum UCH-L1 levels and increase serum GFAP levels in neonates with HIE. Based on their diagnostic value of brain injury, GFAP and UCH-L1 are promising to be novel biomarkers for HIE.

导出引用

蒋曙红, 王金秀, 张一鸣, 蒋惠芬. 亚低温治疗对缺氧缺血性脑病新生儿血清神经胶质酸性蛋白和泛素羧基末端水解酶L1的影响[J]. 中国当代儿科杂志. 2014, 16(12): 1193-1196 https://doi.org/10.7499/j.issn.1008-8830.2014.12.001

JIANG Shu-Hong, WANG Jin-Xiu, ZHANG Yi-Ming, JIANG Hui-Fen. Effect of hypothermia therapy on serum GFAP and UCH-L1 levels in neonates with hypoxic-ischemic encephalopathy[J]. Chinese Journal of Contemporary Pediatrics. 2014, 16(12): 1193-1196 https://doi.org/10.7499/j.issn.1008-8830.2014.12.001

参考文献

[1] 母得志. 新生儿缺氧缺血性脑病的诊断与治疗[J]. 实用儿科临床杂志, 2011, 26(14): 1144-1147.
[2] Douglas-Escobar M, Weiss MD. Biomarkers of brain injury in The premaTure infanT[J]. FronT Neurol, 2012, 3(1): 185-192.
[3] Middeldorp J, Hol EM. GFAP in healTh and disease[J]. Prog Neurobiol, 2011, 93(3): 421-443.
[4] Papa L, Akinyi L, Liu MC, eT al. UbiquiTin C-Terminal hydrolase is a novel biomarker in humans for severe TraumaTic brain injury[J]. CriT Care Med, 2010, 38(1): 138-144.
[5] 中华医学会儿科学新生儿学组. 新生儿缺血缺氧性脑病诊断标准[J]. 中国当代儿科杂志, 2005, 7(2): 97.
[6] 赖燕全, 陈敬华, 龙凤雅. 贝利婴幼儿发育量表对婴幼儿脑瘫康复疗效的评估[J]. 中国妇幼保健, 2008, 23(5): 659-660.
[7] Papa L, Lewis LM, Falk JL, eT a1. ElevaTed levels of serum glialfibfilary acidic proTein breakdown producTs in mild and moderaTe TraumaTic brain injury are associaTed wiTh inTracranial lesions and neurosurgical inTervenTion[J]. Ann Emerg Med, 2012, 59(6): 471-783.
[8] Silver J, Miller JH. RegeneraTion beyond The glial scar[J]. NaT Rev Neurosci, 2004, 5(2): 146-156.
[9] Liu NK, Zhang YP, TiTsworTh WL, eT a1. A nove1 role of phospholipase A2 in mediaTing spinal cord secondary injury[J]. Ann Neurol, 2006, 59(4): 606-619.
[10] FosTer-Barber A, Dickens B, Ferriero DM. Human perinaTal asphyxia: correlaTion of neonaTal cyTokines wiTh MRI and ouTcome[J]. Dev Neurosci, 2001, 23(3): 213-218.
[11] Brophy GM, Mondello S, Papa L, eT a1. BiokineTic analysis of ubiquiTin C-Terminal hydrolase-L1(UCH-L1) in severe TraumaTic brain injury paTienT biofluids[J]. J NeuroTrauma, 2011, 28(6): 86l-870.
[12] Mondello S, LinneT A, Buki A, eT a1. Clinical uTiliTy of serum levels of ubiquiTin C-Terminal hydrolase as a biomarker for severe TraumaTic brain injury[J]. Neurosurgery, 2012, 70(3): 666-675.
[13] Chalak LF, Sanchez PJ, Adams-HueT B, eT al. Biomarkers for severiTy of neonaTal hypoxic-ischemic encephalopaThy and ouTcomes in newborns receiving hypoThermia Therapy[J]. J PediaTr, 2014, 164(3): 468-474.
[14] 蔡清, 薛辛东, 富建华. 新生儿缺氧缺血性脑病研究现状及进展[J]. 中国实用儿科杂志, 2009, 24(12): 968-971.