Page 54 - 南京医科大学学报自然科学版

南京医科大学学报（自然科学版） 第41卷第7期
·984 · Journal of Nanjing Medical University（Natural Sciences） 2021年7月

·基础医学·

生后早期高氧暴露对卵清蛋白诱导支气管哮喘模型小鼠的影响

王 维，朱海艳，郑亚斐，胡晶晶，包天平，田兆方 *
南京医科大学附属淮安第一医院新生儿科，淮安市小儿呼吸重点实验室，江苏 淮安 223300

［摘 要］ 目的：探讨生后早期高氧暴露卵清蛋白（ovalbumin，OVA）诱导支气管哮喘模型小鼠的影响。方法：32 只雌性
BALB/c新生小鼠随机分为4组：空气+PBS组、高氧+PBS组、空气+OVA组、高氧+OVA组，每组8只。高氧+PBS组及高氧+OVA
组小鼠置于高氧箱［氧浓度分数（FiO2 ）≥95%］、空气+PBS组及空气+OVA组置于室内空气（FiO2=21%）中饲养，7 d后4组小鼠同
在空气环境下饲养。6周龄后给予空气+OVA组和高氧+OVA组小鼠腹腔注射混悬致敏液［OVA 1 mg/mL + Al（OH） 3 1 mg/mL］
100 μL致敏及雾化吸入1% OVA激发，同时空气+PBS组和高氧+PBS组给予等量PBS注射；65 d时处死全部动物，进行支气管
肺泡灌洗，留取支气管肺泡灌洗液（broncho alveolar lavage fluid，BALF）行白细胞分类计数，ELISA 法检测BALF 中白细胞介素
（interleukin，IL）⁃5、IL⁃12、IL⁃13水平和血清中IgE 水平；HE染色观察各组小鼠肺组织病理变化。结果：高氧+OVA 组较空气+
OVA组血清IgE水平明显升高（P＜0.05）；BALF中嗜酸性粒细胞、淋巴细胞和单核细胞计数均增加（P＜0.05），IL⁃5、IL⁃13水平
升高而IL⁃12水平降低（P＜0.05）；肺组织病理中大量炎细胞浸润，支气管管腔狭窄，气道壁增厚，气道壁厚度面积占比增加，结
构重塑明显；辐射状肺泡计数明显增加（P＜0.05）。结论：生后早期高氧暴露可加重卵清蛋白诱导的支气管哮喘模型小鼠的气
道炎症反应，气道结构重塑明显，但肺损伤表现减轻。
［关键词］ 支气管哮喘；高氧；细胞因子；小鼠
［中图分类号］ R562.2 ［文献标志码］ A ［文章编号］ 1007⁃4368（2021）07⁃984⁃08
doi：10.7655/NYDXBNS20210708

Effects of early postnatal hyperoxia exposure on ovalbumin ⁃ induced bronchial asthma
model in mice

WANG Wei，ZHU Haiyan，ZHENG Yafei，HU Jingjing，BAO Tianping，TIAN Zhaofang *
Department of Neonatology，the Affiliated Huai’an No.1 People’s Hospital of Nanjing Medical University，the
Pediatric Diagnosis and Treatment Respiratory Key Laboratory of Huai’an，Huai’an 223300，China

［Abstract］ Objective：This study aims to investigate the effects of early postnatal hyperoxia exposure on ovalbumin（OVA）⁃ induced
bronchial asthma mice. Methods：Thirty ⁃ two female BALB/c pups were randomly assigned to four groups：Room Air ⁃ PBS group，
Hyperoxia⁃PBS group，Room Air⁃OVA group，and Hyperoxia⁃OVA group，with 8 mice in each group. Mice in Hyperoxia⁃PBS group and
Hyperoxia⁃OVA group were exposed to hyperoxia（FiO2 ≥ 95%）for 7 days，meanwhile mice in Room Air⁃PBS group and Room Air⁃
OVA group were raised in room air（FiO2 = 21%）. After 7 days，the Hyperoxia⁃PBS group and Hyperoxia⁃OVA group were removed
from hyperoxia and raised in the same environment with the Room Air⁃PBS group and the Room Air⁃OVA group. Mice in Room Air⁃
OVA group and Hyperoxia⁃OVA group were given intraperitoneal injection of sensitization suspension［OVA 1 mg /mL + Al（OH） 3 ］
from d65. All the animals were sacrificed for bronchoalveolar lavage，and the lavage fluid was collected for leukocyte count. The levels
of IL⁃5，IL⁃12，IL⁃13 in bronchoalveolar lavage fluid（BALF）and IgE in serum were measured by ELISA. The lung tissue of mice in
each group was analysis by histological staining for pathological changes. Results：The level of serum IgE in Hyperoxia⁃OVA group
was significantly higher than that in Air ⁃OVA group（P < 0.05）；The counts of eosinophils，lymphocytes and monocytes in BALF were
increased（P < 0.05），the levels of IL⁃5 and IL⁃13 were increased，but the level of IL⁃12 was decreased（P < 0.05）；Inflammatory cells
infiltration，bronchial stenosis，and airway wall thickening were observed，airway wall thickness area ratio was increased（P < 0.05），
structural remodeling was obvious；radial alveolar count（RAC）was increased significantly（P < 0.05）in the Hyperoxia⁃OVA group.

［基金项目］ 淮安市小儿呼吸诊疗重点实验室（HAP201607）
∗
通信作者（Corresponding author），E⁃mail：lyh0729@163.com