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胎儿生长受限发生时血脑屏障完整性是否改变?

Does the Blood-Brain Barrier Integrity Change in Regard to the Onset of Fetal Growth Restriction?

机构信息

Department of Perinatology and Gynecology, Poznan University of Medical Sciences, 60-535 Poznan, Poland.

Department of Neurochemistry and Neuropathology, Poznan University of Medical Sciences, 60-355 Poznan, Poland.

出版信息

Int J Mol Sci. 2023 Jan 19;24(3):1965. doi: 10.3390/ijms24031965.

Abstract

The aim of the study was to determine whether early-onset and late-onset fetal growth restriction (FGR) differentially affects the blood-brain barrier integrity. Furthermore, the purpose of the study was to investigate the relationship between the blood-brain barrier breakdown and neurological disorders in FGR newborns. To evaluate the serum tight junction (TJ) proteins and the placental TJ proteins expression, an ELISA method was used. A significant difference in serum OCLN concentrations was noticed in pregnancies complicated by the early-onset FGR, in relation to the intraventricular hemorrhage (IVH) occurrence in newborns. No significant differences in concentrations of the NR1 subunit of the -methyl-d-aspartate receptor (NR1), nucleoside diphosphate kinase A (NME1), S100 calcium-binding protein B (S100B), occludin (OCLN), claudin-5 (CLN5), zonula occludens-1 (zo-1), the CLN5/zo-1 ratio, and the placental expression of OCLN, CLN5, claudin-4 (CLN4), zo-1 were noticed between groups. The early-onset FGR was associated with a higher release of NME1 into the maternal circulation in relation to the brain-sparing effect and premature delivery. Additionally, in late-onset FGR, the higher release of the S100B into the maternal serum in regard to fetal distress was observed. Furthermore, there was a higher release of zo-1 into the maternal circulation in relation to newborns' moderate acidosis in late-onset FGR. Blood-brain barrier disintegration is not dependent on pregnancy advancement at the time of FGR diagnosis. NME1 may serve as a biomarker useful in the prediction of fetal circulatory centralization and extremely low birth weight in pregnancies complicated by the early-onset FGR. Moreover, the serum zo-1 concentration may have prognostic value for moderate neonatal acidosis in late-onset FGR pregnancies.

摘要

本研究旨在确定早发型和晚发型胎儿生长受限(FGR)是否会对血脑屏障完整性产生不同影响。此外,本研究旨在探讨 FGR 新生儿血脑屏障破裂与神经发育障碍之间的关系。为了评估血清紧密连接(TJ)蛋白和胎盘 TJ 蛋白的表达,采用 ELISA 法。在伴有早发型 FGR 的妊娠中,血清 OCLN 浓度与新生儿脑室出血(IVH)的发生有显著差异。 -甲基-D-天冬氨酸受体(NR1)NR1 亚单位、核苷二磷酸激酶 A(NME1)、S100 钙结合蛋白 B(S100B)、occludin(OCLN)、claudin-5(CLN5)、zonula occludens-1(zo-1)、CLN5/zo-1 比值以及胎盘 OCLN、CLN5、claudin-4(CLN4)、zo-1 的表达在各组之间均无显著差异。早发型 FGR 与母体循环中 NME1 释放增加有关,这与脑保护作用和早产有关。此外,在晚发型 FGR 中,胎儿窘迫时母体血清中 S100B 释放增加。此外,在晚发型 FGR 中,新生儿酸中毒时 zo-1 向母体循环的释放增加。血脑屏障的破坏与 FGR 诊断时的妊娠进展无关。NME1 可作为预测早发型 FGR 中胎儿循环中心化和极低出生体重的有用生物标志物。此外,血清 zo-1 浓度可能对晚发型 FGR 妊娠中新生儿酸中毒具有预后价值。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d19/9916066/c00dd89ee58f/ijms-24-01965-g001.jpg

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