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成年小鼠新生儿期高氧的长期影响

Long-Term Effects of Neonatal Hyperoxia in Adult Mice.

作者信息

Kumar Vasantha H S, Wang Huamei, Kishkurno Sergei, Paturi Babu S, Nielsen Lori, Ryan Rita M

机构信息

Department of Pediatrics, University at Buffalo, Buffalo, New York.

Department of Pediatrics, Medical University of South Carolina, Charleston, South Carolina.

出版信息

Anat Rec (Hoboken). 2018 Apr;301(4):717-726. doi: 10.1002/ar.23766. Epub 2018 Jan 10.

DOI:10.1002/ar.23766
PMID:29281864
Abstract

The outcomes of premature infants have improved greatly; however, the health risks in adulthood are still relatively unclear. Bronchopulmonary dysplasia (BPD) in premature infants is a major risk factor for alteration in lung function and predisposition to respiratory morbidity, and is associated with hyperoxia. The study explores the effect of neonatal hyperoxia on organ systems in adult mice. Newborn mouse litters were randomized to 85%O or room air (RA) on P3 for 12 days; mice were sacrificed at P3, P7, P15, 3 months and 9 months. Lungs were assessed by histopathology, radial alveolar count, mean linear intercept, and α-Smooth muscle actin immunohistochemistry. Aortic assessment included histology, wall thickness, elastin, and collagen content. Glomerular histology and nephron number were assessed in the kidneys. Hyperoxia-exposed mice had progressive alveolar simplification and poor weight gain over time. Greater thickness of pulmonary arterioles by 3 months and a higher Fulton index by 9 months suggest worsening pulmonary hypertension. Aortic wall thickness to lumen ratio was greater with a lower aortic elastin-to-collagen ratio suggesting long-term effects of neonatal hyperoxia. Hyperoxia-exposed mice at 9 months had smaller glomeruli as indicated by glomerular diameter and volume. Prolonged neonatal hyperoxia during the critical period of development induces irreversible lung damage, pulmonary hypertension and structural changes in the kidneys and aorta in adult mice. This could have implications for chronic adult diseases following exposure to high levels of oxygen in the newborn period. Anat Rec, 301:717-726, 2018. © 2017 Wiley Periodicals, Inc.

摘要

早产儿的预后已得到极大改善;然而,其成年后的健康风险仍相对不明。早产儿支气管肺发育不良(BPD)是肺功能改变和易患呼吸系统疾病的主要危险因素,且与高氧有关。本研究探讨新生儿高氧对成年小鼠器官系统的影响。新生小鼠幼崽在出生后第3天被随机分为85%氧气组或空气组(RA),持续12天;在出生后第3天、第7天、第15天、3个月和9个月处死小鼠。通过组织病理学、肺泡计数、平均线性截距和α-平滑肌肌动蛋白免疫组织化学评估肺脏。主动脉评估包括组织学、壁厚、弹性蛋白和胶原蛋白含量。评估肾脏的肾小球组织学和肾单位数量。随着时间推移,暴露于高氧的小鼠出现渐进性肺泡简化和体重增加不佳。3个月时肺小动脉厚度增加,9个月时富尔顿指数升高,提示肺动脉高压加重。主动脉壁厚度与管腔比值增大,主动脉弹性蛋白与胶原蛋白比值降低,提示新生儿高氧的长期影响。9个月时暴露于高氧的小鼠肾小球直径和体积显示肾小球较小。在发育关键期延长新生儿高氧暴露会导致成年小鼠出现不可逆的肺损伤、肺动脉高压以及肾脏和主动脉的结构改变。这可能对新生儿期暴露于高氧后成年期的慢性疾病产生影响。《解剖学记录》,301:717 - 726,2018年。© 2017威利期刊公司。

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