Ben-Ari J, Makhoul I R, Dorio R J, Buckley S, Warburton D, Walker S M
Division of Neonatology, Childrens Hospital Los Angeles, California, USA.
Isr Med Assoc J. 2000 May;2(5):365-9.
Exposure of newborn animals to high concentrations of oxygen leads to diffuse alveolar damage similar to that seen in bronchopulmonary dysplasia in human infants. Therefore, neonatal rats are a suitable practical model of hyperoxic lung damage in human infants.
To determine the involvement of tumor necrosis factor-alpha and interleukin-6 in lung injury in neonatal rats exposed to 100% O2 concentration.
A randomized controlled study was designed in which litters of term Sprague-Dawley rat pups were assigned to experimental or control groups. The pups in the experimental group were placed in 100% O2 from birth for 9 days, while the control pups were placed in room air. Twelve to 15 pups from each group were sacrificed on day 1, 3, 6, 9 and 13 after birth for bronchoalveolar lavage collection and lung histologic study. The bronchoalveolar lavage fluid was assayed for TNF alpha and IL-6.
Newborn rats exposed to 100% O2 for the first 9 days of life showed severe pulmonary edema and hypercellularity on days 1 and 3, which then improved to nearly complete resolution on days 6 and 9. Pulmonary TNF alpha was produced early on O2 exposure (day 3) and pulmonary IL-6 later (days 6 and 9).
Hyperoxia induces sequential production of pulmonary TNF alpha and IL-6, which corresponds to the severity of the pathological findings and the known inflammatory and anti-inflammatory role of these cytokines.
新生动物暴露于高浓度氧气会导致弥漫性肺泡损伤，类似于人类婴儿支气管肺发育不良所见。因此，新生大鼠是人类婴儿高氧性肺损伤的合适实用模型。
确定肿瘤坏死因子-α和白细胞介素-6在暴露于100%氧气浓度的新生大鼠肺损伤中的作用。
设计一项随机对照研究，将足月的斯普拉格-道利大鼠幼崽窝分配到实验组或对照组。实验组幼崽从出生起置于100%氧气环境中9天，而对照幼崽置于室内空气中。在出生后第1、3、6、9和13天，每组处死12至15只幼崽，用于收集支气管肺泡灌洗样本和进行肺组织学研究。对支气管肺泡灌洗液检测肿瘤坏死因子-α和白细胞介素-6。
在出生后的前9天暴露于100%氧气的新生大鼠在第1天和第3天出现严重肺水肿和细胞增多，然后在第6天和第9天改善至几乎完全消退。肺肿瘤坏死因子-α在氧气暴露早期（第3天）产生，肺白细胞介素-6在后期（第6天和第9天）产生。
高氧诱导肺肿瘤坏死因子-α和白细胞介素-6的顺序产生，这与病理结果的严重程度以及这些细胞因子已知的炎症和抗炎作用相对应。
