目的 探讨脑脊液基质金属蛋白酶-9(MMP-9)在不同程度缺氧缺血性脑病(HIE)及其病程中的变化特征。方法 选择HIE患儿60例作为研究对象,根据HIE严重性将其分为轻度、中度和重度HIE组,每组20例。HIE发病后第1、7、14天及第21天为研究时相点,在各时相点采用ELISA夹心法测定脑脊液MMP-9含量,床边监测aEEG;采用观察表记载临床资料。结果 同一严重程度HIE在不同时相点测定的脑脊液MMP-9含量不同,轻度HIE组各时相点之间MMP-9含量比较差异无统计学意义(P>0.05);中度HIE组及重度HIE组各时相点之间MMP-9含量比较差异有统计学意义(P<0.05);同一时相点不同严重程度HIE测定的脑脊液MMP-9含量也不同,第1天MMP-9含量在三组之间两两比较差异均有统计学意义(P<0.05)。在第7天时轻度组和中度组,中度组和重度组之间两两比较差异均有统计学意义(P<0.05)。在第14、21天时,轻度组和重度组之间差异具有统计学意义(P<0.05)。第21天时相点不同预后的MMP-9之间差异有统计学意义(P<0.05),MMP-9含量与HIE预后具有弱相关性(P=0.007)。在第1天、第14天和第21天时相点,MMP-9含量变化与60例HIE具有一定的相关性(P<0.05)。结论 脑脊液MMP-9含量与HIE的病情严重性相关联,MMP-9可作为预报HIE早期诊治、预测预后的指标。
Abstract
Objective To explore the change characteristics of the cerebrospinal fluids matrix metalloproteinase-9 (MMP-9) in different severity levels of hypoxic-ischemic encephalopathy (HIE). Method Totally 60 HIE child patients were selected as the subjects and they were divided into three groups:the mild group,the moderate group and the severe group in terms of the severity,20 patients in each group.The 1st,7th,14th and 21st day were the time points after the seizure,the ELISA method was employed to detect the levels of MMP-9.Electroencephalography (aEEG) was also monitored with an observing table to record the clinical data. Results The detected levels of MMP-9 were different in different time points for the HIE with the same severity.The different levels of MMP-9 in different time points in the HIE mild group showed no statistic significance (P>0.05).The HIE moderate group and the HIE severe group showed statistic significances (P<0.05).The detected levels of MMP-9 were also different at the same time point for the HIE with the different severity.The 1st day MMP-9 levels showed statistic significance (P<0.05) among the three groups.The 7th day showed statistic significance between the mild and moderate group,between the moderate and severe group (P<0.05).The 14th and 21st day showed statistic significance between the mild and severe group (P<0.05).The 21st day showed statistic significance between the MMP-9 with different prognoses (P<0.05),and there was a weak correlation between MMP-9 levels and the HIE prognosis (P=0.007).On the 1st,14th and 21st day,the MMP-9 levels changed in certain correlation with the 60 cases (P<0.05). Conclusions The levels of the cerebrospinal fluids MMP-9 are in correlation with the severity of HIE and can be used as an indicator for the early treatment and prognosis of HIE.
关键词
足月新生儿 /
缺氧缺血性脑病 /
基质金属蛋白酶-9
Key words
full-term newborns /
hypoxic-ischemic encephalopathy /
matrix metalloproteinase-9
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参考文献
[1] Kurinczuk JJ,White-Koning M,Badawi N.Epidemiology of neonatal encephalopathy and hypoxic-ischaemic encephalopathy[J].Early Hum Dev,2010,86(6):329-338.
[2] Gadzinowski J,Gulczyńska E,Michniewicz B,et al.The use of therapeutic whole body cooling in treating hypoxic-ischemic encephalopathy in the newborn the first case in Poland[J].Ginekol Pol,2012,83(8):630-632.
[3] 邵肖梅,叶鸿瑁,丘小汕.实用新生儿学[J].4版.北京:人民卫生出版社,2011:700-706.
[4] Drury PP,Bennet L,Gunn AJ.Mechanisms of hypothermic neuroprotection[J].Semin Fetal Neonatal Med,2010,15:287-292.
[5] Petzold A.Glialfibrillary acidic protein is a body fluid biomarker for glial pathology in human disease[J].Brain Res,2015,1600:17-31.
[6] Bauer AT,Bürgers HF,RabieT,et al.Matrix metalloproteinase-9 mediates hypoxia-induced vascular leakage in the brain via tight junction rearrangement[J].J Cereb Blood Flow Metab,2010,30(4):837-48.
[7] Teunissen CE,TumaniH,BennettJL,et al.Consensus Guidelines for CSF and Blood Biobanking for CNS Biomarker Studies[J].Mult Scler Int,2011,18(6):e1-9.
[8] ShalakL,PerlmanJM.Hypoxic-ischemic brain injury in the term infant-current concepts[J].Early Hum Dev,2004,80(20):125-141.
[9] 王钰,尹晓娟.新生儿缺氧缺血性脑损伤潜在的靶向治疗[J].中华临床医师杂志,2013,28(5),352-355.
[10] DupontTL,ChalakLF,Morriss MC,et al.Short-term outcomes of newborns with perinatal acidemia who are not eligible for systemic hypothermia therapy[J].J Pediatr,2013,162(1):35-41.
[11] Savage WJ,EverettAD.Biomarkers in pediatrics:children as biomarker orphans[J].Proteomics Clin Appl,2010,4(12):915-921.
[12] Nissi R,Talvensaari-Mattila A,Kotila V,et al.Circulating matrix metalloproteinase MMP-9 and MMP-2/TIMP-2 complex are associated with spontaneous early pregnancyfailure[J].Reprod Biol Endocrinol,2013,11(2):e1-6.
[13] Brackmann FA,Link AS,Jung S,et al.Activin A regulation under global hypoxia in developing mouse brain[J].Brain Res,2013,1531(19):65-74.