Department of Paediatrics and Child Health, University College Cork, Cork, Ireland.
INFANT Centre, University College Cork, Cork, Ireland.
Mol Neurobiol. 2019 May;56(5):3657-3663. doi: 10.1007/s12035-018-1321-4. Epub 2018 Sep 3.
Hypoxic-ischaemic encephalopathy (HIE) remains one of the leading causes of neurological disability worldwide. No blood biomarker capable of early detection and classification of injury severity in HIE has been identified. This study aimed to investigate the potential of miRNA-181b (miR-181b) and its downstream target, ubiquitin C-terminal hydrolase-L1 (UCH-L1), to predict the severity of HIE. Full-term infants with perinatal asphyxia were recruited at birth and observed for the development of HIE, along with healthy controls. Levels of miR-181b and messenger UCH-L1 (mUCH-L1) in umbilical cord blood were determined using qRT-PCR. In total, 131 infants; 40 control, 50 perinatal asphyxia without HIE (PA) and 41 HIE, recruited across two separate cohorts (discovery and validation) were included in this study. Significant and consistent downregulation of miR-181b was observed in infants with moderate/severe HIE compared to all other groups in both cohorts: discovery 0.25 (0.16-0.32) vs 0.61 (0.26-1.39), p = 0.027 and validation 0.33 (0.15-1.78) vs 1.2 (0.071-2.09), p = 0.035. mUCH-L1 showed increased expression in infants with HIE in both cohorts. The expression ratio of miR-181b to mUCH-L1 was reduced in those infants with moderate/severe HIE in both cohorts: discovery cohort 0.23 (0.06-0.44) vs 1.59 (0.46-2.54), p = 0.01 and validation cohort 0.41 (0.10-0.81) vs 1.38 (0.59-2.56) in all other infants, p = 0.009. We have validated consistent patterns of altered expression in miR-181b/mUCH-L1 in moderate/severe neonatal HIE which may have the potential to guide therapeutic intervention in HIE.
缺氧缺血性脑病（HIE）仍然是全球导致神经功能障碍的主要原因之一。目前尚未发现能够早期检测和分类 HIE 损伤严重程度的血液生物标志物。本研究旨在探讨 microRNA-181b（miR-181b）及其下游靶标泛素 C 末端水解酶-L1（UCH-L1）预测 HIE 严重程度的潜力。在出生时招募患有围产期窒息的足月婴儿，并观察其 HIE 发展情况，同时设置健康对照组。使用 qRT-PCR 测定脐带血中 miR-181b 和信使 UCH-L1（mUCH-L1）的水平。本研究共纳入了来自两个独立队列（发现队列和验证队列）的 131 名婴儿；40 名对照组、50 名围产期窒息但无 HIE（PA）组和 41 名 HIE 组。在两个队列中，与所有其他组相比，中度/重度 HIE 婴儿的 miR-181b 表达均显著下调：发现队列中 0.25（0.16-0.32）vs 0.61（0.26-1.39），p=0.027；验证队列中 0.33（0.15-1.78）vs 1.2（0.071-2.09），p=0.035。在两个队列中，HIE 婴儿的 mUCH-L1 表达均增加。在两个队列中，中度/重度 HIE 婴儿的 miR-181b 与 mUCH-L1 的表达比值均降低：发现队列中 0.23（0.06-0.44）vs 1.59（0.46-2.54），p=0.01；验证队列中 0.41（0.10-0.81）vs 1.38（0.59-2.56），p=0.009。我们已经验证了 miR-181b/mUCH-L1 在中度/重度新生儿 HIE 中的一致改变表达模式，这可能具有指导 HIE 治疗干预的潜力。
