新生儿大鼠肝组织病理学、IGF-1、IGFBP-3和GHBP的高氧或常氧解决间歇性缺氧和间歇性高氧发作的比较

IF 1.6 4区 医学 Q4 CELL BIOLOGY
Charles L. Cai , Matthew Marcelino , Jacob V. Aranda , Kay D. Beharry
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引用次数: 0

摘要

目的因慢性肺病需要氧气治疗的极低胎龄新生儿在生命的最初几周内,动脉血氧饱和度或间歇性缺氧(IH)会反复波动。这些事件与生长发育迟缓、高血压和晚年胰岛素抵抗的高风险有关。这项研究验证了IH或间歇性高氧对肝脏有类似负面影响的假设;体细胞生长;和肝胰岛素样生长因子(IGF)-I、IGF结合蛋白(BP)-3和生长激素结合蛋白(GHBP),无论发作之间的常氧或高氧消退。设计新生大鼠在出生第一天(P0)暴露于两种IH模式:1)高氧(50%O2)伴短暂缺氧(12%O2);或2)常氧(21%O2)伴缺氧(12%O2);间歇性缺氧(50%O2/21%O2);仅高氧(50%O2);或室内空气(RA,21%O2)。幼犬在P14被安乐死或置于RA中直到P21。对照组从P0-P21起仍处于RA。评估生长、肝脏组织病理学、细胞凋亡、IGFI、IGFBP-3和GHBP。结果IH组和间歇性高氧组肝细胞的病理学表现,包括细胞肿胀、脂肪变性、凋亡、坏死和局灶性血窦充血,尤其是暴露期间21-12%O2组(P14),在恢复/复氧期间(P21)没有显著改善。这些作用与HIF1α的诱导以及肝脏IGFI、IGFBP-3和GHBP的减少有关。结论无论RA或高氧消退,在生命的最初几周暴露于IH或间歇性高氧对未成熟肝脏都是有害的。这些发现可能表明,预防新生儿早期血氧饱和度频繁波动的干预措施仍然是当务之急。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Comparison of hyperoxia or normoxia resolution of intermittent hypoxia and intermittent hyperoxia episodes on liver histopathology, IGF-1, IGFBP-3, and GHBP in neonatal rats

Objective

Extremely low gestational age neonates requiring oxygen therapy for chronic lung disease experience repeated fluctuations in arterial oxygen saturation, or intermittent hypoxia (IH), during the first few weeks of life. These events are associated with a high risk for reduced growth, hypertension, and insulin resistance in later life. This study tested the hypothesis that IH, or intermittent hyperoxia have similar negative effects on the liver; somatic growth; and liver insulin-like growth factor (IGF)-I, IGF binding protein (BP)-3, and growth hormone binding protein (GHBP), regardless of resolution in normoxia or hyperoxia between episodes.

Design

Newborn rats on the first day of life (P0) were exposed to two IH paradigms: 1) hyperoxia (50% O2) with brief hypoxia (12% O2); or 2) normoxia (21% O2) with hypoxia (12% O2); intermittent hypoxia (50% O2/21% O2); hyperoxia only (50% O2); or room air (RA, 21% O2). Pups were euthanized on P14 or placed in RA until P21. Controls remained in RA from P0-P21. Growth, liver histopathology, apoptosis, IGFI, IGFBP-3, and GHBP were assessed.

Results

Pathological findings of the liver hepatocytes, including cellular swelling, steatosis, apoptosis, necrosis and focal sinusoid congestion were seen in the IH and intermittent hyperoxia groups, and were particularly severe in the 21–12% O2 group during exposure (P14) with no significant improvements during recovery/reoxygenation (P21). These effects were associated with induction of HIF, and reductions in liver IGFI, IGFBP-3, and GHBP.

Conclusions

Exposure to IH or intermittent hyperoxia during the first few weeks of life regardless of resolution in RA or hyperoxia is detrimental to the immature liver. These findings may suggest that interventions to prevent frequent fluctuations in oxygen saturation during early neonatal life remain a high priority.

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来源期刊
Growth Hormone & Igf Research
Growth Hormone & Igf Research 医学-内分泌学与代谢
CiteScore
3.30
自引率
0.00%
发文量
38
审稿时长
57 days
期刊介绍: Growth Hormone & IGF Research is a forum for research on the regulation of growth and metabolism in humans, animals, tissues and cells. It publishes articles on all aspects of growth-promoting and growth-inhibiting hormones and factors, with particular emphasis on insulin-like growth factors (IGFs) and growth hormone. This reflects the increasing importance of growth hormone and IGFs in clinical medicine and in the treatment of diseases.
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