Morphological characterization of pulmonary microvascular disease in bronchopulmonary dysplasia caused by hyperoxia in newborn mice
Morphological characterization of pulmonary microvascular disease in bronchopulmonary dysplasia caused by hyperoxia in newborn mice
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DOI：
10.1007/s00795-018-0182-2
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发表时间：
2018-01
影响因子：
1.8
通讯作者：
H. Nakanishi;S. Morikawa;Shuji Kitahara;Asuka Yoshii;A. Uchiyama;S. Kusuda;T. Ezaki
中科院分区：
文献类型：
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作者：
H. Nakanishi;S. Morikawa;Shuji Kitahara;Asuka Yoshii;A. Uchiyama;S. Kusuda;T. Ezaki
目的肺微血管损伤与支气管肺发育不良（BPD）的发病机制有关。为了研究BPD引起的肺血管疾病的机制，我们研究了影响肺微血管的超微结构变化。方法将新生ICR小鼠置于85%高氧或常氧条件下14 d，然后在正常换气条件下7 d。在出生后第14天和第21天，取肺进行超微结构检查和评估肺动脉高压。结果高氧暴露肺微血管超微结构显示毛细血管管腔塌陷。这是由于内皮细胞（ECs）的异常形态，其特征是细胞质不均厚。与正常空气对照相比，标本也显示出明显厚的血气屏障（BABs），其中大部分被EC层成分占据。结构改变伴有肺动脉内侧厚度增加和右心室肥厚（RVH）。此外，即使在正常的空气替换条件下暴露7天后，ECs的异常仍然存在。结果经形态计量定量证实。结论毛细血管内皮细胞及厚壁动脉的形态异常与肺动脉重构及RVH有关。这些超微结构变化可能代表了BPD继发性肺动脉高压的可能机制。
PurposePulmonary microvascular injury is associated with the pathogenesis of bronchopulmonary dysplasia (BPD). To characterize the mechanisms of pulmonary vascular disease resulting from BPD, we studied the ultrastructural changes affecting pulmonary microvasculature.MethodsNewborn ICR mice were exposed to 85% hyperoxia or normoxia for 14 days, and then normal air replacement conditions for the following 7 days. At postnatal day (P)14 and P21, lungs were harvested for ultrastructural examination and assessment of pulmonary hypertension.ResultsThe ultrastructure of pulmonary microvasculature in the hyperoxia-exposed lungs revealed a collapsed capillary lumen. This was due to the abnormal morphology of endothelial cells (ECs) characterized by heterogeneously thick cytoplasm. Compared to normal air controls, the specimens displayed also remarkably thick blood–air barriers (BABs), most of which were occupied by EC layer components. Structural changes were accompanied by increased pulmonary artery medial thickness and right ventricular hypertrophy (RVH). Moreover, abnormalities in ECs persisted even after exposure to 7 days of normal air replacement conditions. Results were confirmed by morphometric quantification.ConclusionOur results suggest that the abnormal morphology of capillary ECs and thick BABs correlates with pulmonary artery remodeling and RVH. These ultrastructural changes might represent possible mechanisms of secondary pulmonary hypertension in BPD.