支气管肺发育不良模型小鼠青春期肺部菌群特点  

Characteristics of pulmonary microbiome in adolescent mice model of bronchopulmonary dysplasia

作　　者：李靖燕 曹林霞 马萌萌 胡晶晶 包天平[1] 田兆方[1] LI Jingyan;CAO Linxia;MA Mengmeng;HU Jingjing;BAO Tianping;TIAN Zhaofang(Department of Neonatology,the Affiliated Huaian No.1 People’s Hospit’al of Nanjing Medical University,Huai’an Key Laboratory of Diagnosis and Treatment of Pediatric Respiratory Diseases,Huai’an 223300,China)

机构地区：[1]南京医科大学附属淮安第一医院新生儿科,淮安市小儿呼吸诊疗重点实验室,江苏淮安223300

出　　处：《南京医科大学学报（自然科学版）》2023年第12期1643-1649,共7页Journal of Nanjing Medical University(Natural Sciences)

基　　金：江苏省卫健委重点资助项目(ZDB2020005)。

摘　　要：目的:探究支气管肺发育不良(bronchopulmonary dysplasia,BPD)模型小鼠青春期肺部菌群特点。方法:32只C57BL/6J新生小鼠,分为空气雌性组、空气雄性组、高氧雌性组、高氧雄性组,每组8只。高氧组小鼠生后即置于FiO2>95%的环境中7 d,空气组小鼠置于同室内空气(FiO2=21%)环境;之后所有小鼠室内空气环境下饲养直至6周。苏木精⁃伊红(hema⁃toxylin⁃eosin,HE)染色法观察小鼠肺组织病理变化;16S rDNA测序分析肺组织菌群特点。结果:BPD模型小鼠青春期肺组织肺泡化程度降低(P<0.01),双因素方差分析显示性别对小鼠辐射状肺泡计数(radial alveolar count,RAC)变化无显著差异(F=2.001,P>0.05)。Anosim相似性分析结果显示空气组和高氧组雄性小鼠肺部菌群差异有统计学意义(r=0.906,P=0.03),雌性小鼠菌群差异无统计学意义(r=-0.094,P=0.722)。Alpha多样性结果显示高氧组和空气组的肺部菌群物种丰富度无统计学差异(P>0.05),Beta多样性分析中,PCoA图显示4组肺部菌群存在统计学差异(P<0.05)。LEfSe分析结果显示,高氧组棒状杆菌属(Corynebacterium)丰度下降,葡萄球菌种(Staphylococcus)升高。结论:BPD模型小鼠青春期肺部微生物群失调,棒状杆菌属(Corynebacterium)丰度下降,葡萄球菌种(Staphylococcus)升高,并且菌群失调可能与性别相关。Objective:To explore the pulmonary microbiome characteristics of adolescent mice model of bronchopulmonary dysplasia(BPD).Methods:Thirty⁃two C57BL/6J neonatal mice were divided into air female group,air male group,hyperoxic female group,and hyperoxic male group,with 8 mice in each group.The mice in the hyperoxic group were placed in the environment with FiO2>95%for 7 days immediately after birth,and the mice in the air group were placed in the same indoor air with FiO2=21%.All mice were then raised in indoor air environment until 6 weeks.The pathological changes of lung tissues were observed by hematoxylin⁃eosin staining(HE).The characteristics of pulmonary microbiome were analyzed by 16S rDNA sequencing.Results:The alveolation degree of lung tissue decreased in early hyperoxygen exposure group(P<0.01).Two⁃factor ANOVA showed that radial alveolar count(RAC)had no significant difference between sex in mice(F=2.001,P>0.05).The results of Anosim similarity analysis showed that there was statistical significance in pulmonary microbiome of male mice in the air group and the high oxygen group(r=0.906,P=0.03),while there was no statistical significance in the female mice(r=-0.0938,P=0.722).Alpha diversity results showed that there was no statistical difference in the species richness of lung flora between the high oxygen group and the air group(P>0.05),and in the analysis of Beta diversity,PCoA diagram showed that there were statistical differences in lung flora among the four groups(P<0.05).LEfSe analysis showed that the abundance of Corynebacterium in the high oxygen group decreased and Staphylococcus increased.Conclusion:The lung microbiota of adolescent mice in the BPD model are disregulated,with a decrease in the abundance of Corynebacterium,and an increase in Staphylococcus,and the microbiota imbalance might be related to gender.

关 键 词：支气管肺发育不良 肺部菌群 16S rDNA 小鼠 

分 类 号：R725.6[医药卫生—儿科]