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不同孕周新生儿氧化应激标志物与内皮素-1水平的关系

Relationship Between Oxidative Stress Markers and Endothelin-1 Levels in Newborns of Different Gestational Ages.

作者信息

Stefanov Gospodin, Briyal Seema, Pais Gwendolyn, Puppala Bhagya, Gulati Anil

机构信息

Division of Neonatology, Advocate Children's Hospital, Park Ridge, IL, United States.

Chicago College of Pharmacy, Midwestern University, Downers Grove, IL, United States.

出版信息

Front Pediatr. 2020 Jun 2;8:279. doi: 10.3389/fped.2020.00279. eCollection 2020.

Abstract

Oxidative stress results from excessive reactive oxygen species formation and/or inadequate antioxidant defense. Premature and critically ill infants are especially susceptible due to an immature intrinsic antioxidant system that cannot fully compensate for a free radical load. Oxidative stress is also associated with endothelial dysfunction and alterations in Endothelin-1 (ET-1) signaling pathways. However, the effects of the complex interaction between oxidative stress and ET-1 in newborns are not well-understood. The objective of this pilot study was to determine the relationship between levels of common oxidative stress biomarkers [glutathione (GSH), malondialdehyde (MDA)] and ET-1 in newborns of different gestational ages. In a level IV NICU, 63 neonates were prospectively enrolled and divided into groups based on gestational age at birth: Early Preterm (24 0/7-30 6/7 weeks), Late Preterm (31 0/7-36 6/7 weeks), and Term (37 0/7-42 weeks). Umbilical cord (1.5 mL) and 24(±4) h of life (24 h) (1 mL) blood samples were collected for GSH, MDA, and ET-1 analyses. GSH, MDA, and ET-1 were determined using established methodology. Mean cord MDA levels for all age groups, Early Preterm (2.93 ± 0.08 pg/ml), Late Preterm (2.73 ± 0.15 pg/ml), and Term (2.92 ± 0.13 pg/ml), were significantly higher than those at 24 h of life ( < 0.001). Mean cord ET-1 levels were significantly higher than 24 h samples in both Early and Late Preterm groups ( < 0.05). Cord and 24 h ET-1 levels did not correlate with MDA and GSH levels at birth (r = 0.03, > 0.05 and r = 0.001, > 0.05, respectively) or 24 h of life (r = 0.001, > 0.05 and r = 0.03, > 0.05, respectively). Preterm neonates exposed to prenatal corticosteroids (1.87 ± 0.31 pg/ml) had lower cord MDA levels than non-exposed neonates (2.85 ± 0.12 pg/ml) ( < 0.05). Both cord and 24 h OS markers were significantly higher in neonates treated with oxygen therapy ( < 0.005 and < 0.05, respectively) than those who did not receive supplemental oxygen. Oxidative stress markers (MDA and GSH) and ET-1 levels act independently. MDA is higher in cord blood than at 24 h of life regardless of gestational age. In preterm neonates, ET-1 levels are higher in umbilical cord blood compared to 24 h of life.

摘要

氧化应激源于活性氧的过度生成和/或抗氧化防御不足。早产和危重症婴儿尤其易感,因为其内在抗氧化系统不成熟,无法完全代偿自由基负荷。氧化应激还与内皮功能障碍以及内皮素-1(ET-1)信号通路改变有关。然而,氧化应激与ET-1在新生儿中的复杂相互作用的影响尚未完全明确。本初步研究的目的是确定不同胎龄新生儿中常见氧化应激生物标志物[谷胱甘肽(GSH)、丙二醛(MDA)]水平与ET-1之间的关系。在一家四级新生儿重症监护病房,前瞻性纳入63例新生儿,并根据出生时的胎龄分为几组:极早产儿(24⁰/₇ - 30⁶/₇周)、晚期早产儿(31⁰/₇ - 36⁶/₇周)和足月儿(37⁰/₇ - 42周)。采集脐带血(1.5 mL)和出生后24(±4)小时(24小时)的血样(1 mL)用于GSH、MDA和ET-1分析。使用既定方法测定GSH、MDA和ET-1。所有年龄组的脐带血MDA平均水平,极早产儿(2.93±0.08 pg/ml)、晚期早产儿(2.73±0.15 pg/ml)和足月儿(2.92±0.13 pg/ml),均显著高于出生后24小时(P<0.001)。极早产儿和晚期早产儿组的脐带血ET-1平均水平均显著高于24小时样本(P<0.05)。脐带血和出生后24小时的ET-1水平与出生时(r = 0.03,P>0.05和r = 0.001,P>0.05,分别)或出生后24小时(r = 0.001,P>0.05和r = 0.03,P>0.05,分别)的MDA和GSH水平均无相关性。暴露于产前糖皮质激素治疗的早产儿(1.87±0.31 pg/ml)脐带血MDA水平低于未暴露的新生儿(2.85±0.12 pg/ml)(P<0.05)。接受氧疗的新生儿脐带血和出生后24小时的氧化应激标志物均显著高于未接受补充氧气的新生儿(分别为P<0.005和P<0.05)。氧化应激标志物(MDA和GSH)与ET-1水平独立发挥作用。无论胎龄如何,脐带血中的MDA均高于出生后24小时。在早产儿中,脐带血中的ET-1水平高于出生后24小时。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/730d/7280445/8b1e3519ca2e/fped-08-00279-g0001.jpg

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