徐凤丹　+王优　吴文燊　谢松敏

[摘要] 目的 觀察高氧暴露对新生小鼠肺部炎性反应及纤维化的影响。 方法 新生2日龄昆明小鼠40只，随机分为空气组（n = 20）及高氧组（n = 20），分别在空气或（60±5）%氧气中饲养。每天检测小鼠状态，隔天记录小鼠体重情况。在实验第3、7、14、21天，每组各取5只小鼠处死，观察肺组织外观、计算肺组织湿/干重比值；HE染色观察肺组织病理结构；天狼星红染色观察肺组织胶原纤维情况。 结果 ①实验过程中两组均未出现小鼠死亡；高氧组小鼠高氧暴露后第7天开始体重明显低于空气组，差异有高度统计学意义（P < 0.01）。②高氧暴露后第7天开始，小鼠肺湿重/干重比值均高于空气组，差异有统计学意义（P < 0.05或P < 0.01）。③高氧组肺部结构随高氧暴露时间的增加逐渐出现典型支气管肺发育不良（BPD）样表现：肺泡呈不规则结构，腔隙较大，部分肺泡融合，整体数量减少，部分区域有炎性不张；高氧暴露后第14、21天，高氧组辐射状肺泡计数（RAC）低于空气组，差异有高度统计学意义（P < 0.01）。④高氧暴露后第7、14、21天，高氧组肺部胶原面积较空气组显著增加。 结论 持续高氧暴露可成功制作BPD小鼠模型；持续高氧暴露后可导致新生小鼠肺部炎性反应及纤维化增加，可能是BPD发生的重要机制。

[关键词] 支气管肺发育不良；新生小鼠；高氧暴露；炎性反应；纤维化

[中图分类号] R722.6 [文献标识码] A [文章编号] 1673-7210（2017）09（b）-0021-04

Effects of hyperoxia on pulmonary inflammation and fibrosis in newborn mice

XU Fengdan1，2 WANG You1 WU Wenshen2 XIE Songmin2

1.Department of Pediatrics， Guangdong Medical University， Guangdong Province， Dongguan 523808， China； 2.NICU， Dongguan Eighth People's Hospital， Guangdong Province， Dongguan 523235， China

[Abstract] Objective To observe the effects of hyperoxia exposure on pulmonary inflammatory response and fibrosis in new born mice. Methods 40 Kunming mice aged 2 days were randomly divided into air group （n = 20） and hyperoxia group （n = 20）， reared in air or （60±5）% oxygen respectively. The mice were examined daily and the weight was recorded the next day. At the 3rd， 7th， 14th， 21st day of the experiment， 5 mice of each group were sacrificed respectively， then the appearance of lung tissue， lung wet/dry weight ratio were observed； the pathological structure of lung tissue was examination by HE staining； collagen fiber of lung tissue was examination by Sirius red staining. Results ①No mouse died in the two groups during the experiment. The weight of mousein hyperoxia group was significantly was lower than that of air group at the 7th day after exposured to oxygen， the difference was statistically significant （P < 0.01）. ②The ratio of lung wet/dry weight in hyperoxia group was higher than that in air-group begin the 7th day after hyperoxia exposured， the difference was statistically significant （P < 0.05 or P < 0.01）. ③In hyperoxia group， with the time of exposured to oxygen increasing， lung structure showed typical BPD： alveoli showed irregular structure， interstitial was large， partial alveoli fused， alveolar count decreased， partial region occured inflammatory closed； at the 14th， 21st day after hyperoxia exposured， RAC in hyperoxia group was lower than air group， the difference was statistically significant （P < 0.01）. ④Compared with air group， collagen area in hyperoxia-group increased at yhe 7th， 14th， 21st day after hyperoxia exposured. Conclusion BPD micemodels were successfully produced by sustained hyperoxia exposure. Sustained hyperoxia exposure may increase lung inflammation and fibrosis in neonatal mice， which may be an important mechanism for the development of BPD.endprint

[Key words] Bronchopulmonary dysplasia； Newborn rats； Hyporoxia； Inflammation； Fibrosis

支气管肺发育不良（BPD），又称新生儿慢性肺病（CLD），于1976年由Northway等[1]首次提出，是早产儿常见的慢性疾病，是吸氧和机械通气治疗早产儿后最常见的并发症[2]。随着医疗水平的提高，尽管早产儿存活率增加，但BPD发病率有逐年增加的趋势，然而目前BPD的发病机制仍未完全明确，也缺乏有效防治方法[3-4]。成功建立动物BPD模型是临床研究BPD发病机制的重要基础，本文通过高氧暴露方法制作了BPD小鼠模型，并对肺组织炎性反应及纤维化情况进行了初步观察，为进一步探讨BPD发病机制及防治方法提供良好的实验基础。

1 材料与方法

1.1 实验动物

2日龄新生昆明小鼠40只，平均体重为（2.18±0.18）g，雌雄不限，购自军事医学科学院（动物合格证号：0026757）。

1.2 仪器及试剂

自制封闭聚乙烯高氧饲养箱、医用氧气瓶……