Cai Charles L, Marcelino Matthew, Aranda Jacob V, Beharry Kay D
Department of Pediatrics, Division of Neonatal-Perinatal Medicine, State University of New York, Downstate Medical Center, Brooklyn, NY 11203, USA.
Department of Pediatrics, Division of Neonatal-Perinatal Medicine, State University of New York, Downstate Medical Center, Brooklyn, NY 11203, USA; Department of Ophthalmology; State University of New York, Downstate Medical Center, Brooklyn, NY 11203, USA.
Growth Horm IGF Res. 2023 Oct-Dec;72-73:101559. doi: 10.1016/j.ghir.2023.101559. Epub 2023 Sep 9.
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.
Newborn rats on the first day of life (P0) were exposed to two IH paradigms: 1) hyperoxia (50% O) with brief hypoxia (12% O); or 2) normoxia (21% O) with hypoxia (12% O); intermittent hypoxia (50% O/21% O); hyperoxia only (50% O); or room air (RA, 21% O). 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.
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% O 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.
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.
患有慢性肺病且需要吸氧治疗的极早产儿在出生后的头几周会出现动脉血氧饱和度反复波动，即间歇性缺氧（IH）。这些情况与日后生长发育迟缓、高血压和胰岛素抵抗的高风险相关。本研究检验了以下假设：无论发作期间的常氧或高氧状态是否缓解，间歇性缺氧（IH）或间歇性高氧对肝脏、躯体生长以及肝脏胰岛素样生长因子（IGF）-I、IGF结合蛋白（BP）-3和生长激素结合蛋白（GHBP）均有类似的负面影响。
新生大鼠在出生第一天（P0）暴露于两种间歇性缺氧模式：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）。幼崽在P14时实施安乐死，或置于室内空气中直至P21。对照组从P0到P21一直置于室内空气中。评估生长、肝脏组织病理学、细胞凋亡、IGFI、IGFBP - 3和GHBP。
在间歇性缺氧和间歇性高氧组中观察到肝肝细胞的病理表现，包括细胞肿胀、脂肪变性、细胞凋亡、坏死和局灶性窦状充血，在暴露期间（P14）的21 - 12% O₂组中尤为严重，在恢复/再氧合期间（P21）无明显改善。这些影响与低氧诱导因子的诱导以及肝脏IGFI、IGFBP - 3和GHBP的降低有关。
出生后头几周暴露于间歇性缺氧或间歇性高氧，无论在室内空气或高氧状态下是否缓解，均对未成熟肝脏有害。这些发现可能表明，采取干预措施防止新生儿早期血氧饱和度频繁波动仍然是一项高度优先事项。
