Lei Jun, Paules Cristina, Nigrini Elisabeth, Rosenzweig Jason M, Bahabry Rudhab, Farzin Azadeh, Yang Samuel, Northington Frances J, Oros Daniel, McKenney Stephanie, Johnston Michael V, Graham Ernest M, Burd Irina
Integrated Research Center for Fetal Medicine, Department of Gynecology and Obstetrics, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Aragón Health Research Institute, SAMID Network ref RD12/0026/001, Zaragoza, Spain.
Front Pediatr. 2017 May 22;5:112. doi: 10.3389/fped.2017.00112. eCollection 2017.
There are no definitive markers to aid in diagnosis of neonatal encephalopathy (NE). The purpose of our study was (1) to identify and evaluate the utility of neuronal nitric oxide synthase (NOS1) in umbilical cord blood as a NE biomarker and (2) to identify the source of NOS1 in umbilical cord blood.
This was a nested case-control study of neonates >35 weeks of gestation. ELISA for NOS1 in umbilical cord blood was performed. Sources of NOS1 in umbilical cord were investigated by immunohistochemistry, western blot, ELISA, and quantitative PCR. Furthermore, umbilical cords of full-term neonates were subjected to 1% hypoxia .
NOS1 was present in umbilical cord blood and increased in NE cases compared with controls. NOS1 was expressed in endothelial cells of the umbilical cord vein, but not in artery or blood cells. In experiments, hypoxia was associated with increased levels of NOS1 in venous endothelial cells of the umbilical cord as well as in culture medium.
This is the first study to investigate an early marker of NE. NOS1 is elevated with hypoxia, and further studies are needed to investigate it as a valuable tool for early diagnosis of neonatal brain injury.
目前尚无明确的标志物可辅助新生儿脑病(NE)的诊断。我们研究的目的是:(1)识别并评估脐带血中神经元型一氧化氮合酶(NOS1)作为NE生物标志物的效用;(2)确定脐带血中NOS1的来源。
这是一项对孕周>35周的新生儿进行的巢式病例对照研究。对脐带血中的NOS1进行酶联免疫吸附测定(ELISA)。通过免疫组织化学、蛋白质印迹法、ELISA和定量聚合酶链反应(PCR)研究脐带中NOS1的来源。此外,对足月新生儿的脐带进行1%的低氧处理。
脐带血中存在NOS1,与对照组相比,NE病例中的NOS1增加。NOS1在脐带静脉内皮细胞中表达,但在动脉或血细胞中不表达。在实验中,低氧与脐带静脉内皮细胞以及培养基中NOS1水平的升高有关。
这是第一项研究NE早期标志物的研究。NOS1随低氧而升高,需要进一步研究以考察其作为新生儿脑损伤早期诊断的有价值工具的作用。