Effects of hyperoxia on alveolar and pulmonary vascular development in germ-free mice
Effects of hyperoxia on alveolar and pulmonary vascular development in germ-free mice
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DOI：
10.1152/ajplung.00316.2019
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发表时间：
2020-02-01
影响因子：
4.9
通讯作者：
Lal, Charitharth Vivek
中科院分区：
文献类型：
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作者：
Dolma, Kalsang;Freeman, Amelia E.;Lal, Charitharth Vivek
呼吸道微生物生态失调与极早产儿随后发生的支气管肺发育不良（BPD）有关。然而，气道微生物组在正常肺发育中的关系尚未确定。为了更好地理解气道微生物组的作用，我们比较了有或没有微生物组的小鼠的正常和异常肺泡和肺血管发育。我们假设，与非无菌（NGF）小鼠相比，无菌（GF）小鼠的肺部对高氧的表型反应会更大。使用一种新的非生物高氧室，GF和NGF小鼠暴露于常氧或高氧。研究了肺泡形态学、肺力学、超声心动图、炎症标志物和肺动脉高压的测量。GF和NGF小鼠在常氧下没有差异，而GF小鼠在高氧下显示保护肺结构和力学，并减少炎症标记物与NGF小鼠相比。我们推测NGF小鼠体内病原菌丰度的增加可能通过调节肺部的促炎信号和嗜酸性炎症在BPD发病机制中发挥作用。气道微生物组的操纵可能是BPD和其他肺部疾病的潜在治疗干预。
Airway microbial dysbiosis is associated with subsequent bronchopulmonary dysplasia (BPD) development in very preterm infants. However, the relationship of airway microbiome in normal pulmonary development has not been defined. To better understand the role of the airway microbiome, we compared normal and abnormal alveolar and pulmonary vascular development in mice with or without a microbiome. We hypothesized that the lungs of germ-free (GF) mice would have an exaggerated phenotypic response to hyperoxia compared with non-germ-free (NGF) mice. With the use of a novel gnotobiotic hyperoxia chamber, GF and NGF mice were exposed to either normoxia or hyperoxia. Alveolar morphometry, pulmonary mechanics, echocardiograms, inflammatory markers, and measures of pulmonary hypertension were studied. GF and NGF mice in normoxia showed no difference, whereas GF mice in hyperoxia showed protected lung structure and mechanics and decreased markers of inflammation compared with NGF mice. We speculate that an increase in abundance of pathogenic bacteria in NGF mice may play a role in BPD pathogenesis by regulating the proinflammatory signaling and neutrophilic inflammation in lungs. Manipulation of the airway microbiome may be a potential therapeutic intervention in BPD and other lung diseases.