Pulmonary Hypoplasia Resulting from Pulmonary Artery Banding in Infancy: A Neonatal Rat Model Study
Pulmonary Hypoplasia Resulting from Pulmonary Artery Banding in Infancy: A Neonatal Rat Model Study
复制标题
DOI：
10.1007/s00246-020-02495-9
复制
发表时间：
2020-11-05
影响因子：
1.6
通讯作者：
Zheng, Jinghao
中科院分区：
文献类型：
--
作者：
Luo, Qiancheng;Xu, Xiuxia;Zheng, Jinghao
本研究旨在建立新生儿大鼠肺血流量减少（PBF）模型，研究肺血流量减少对新生儿肺发育的病理生理影响。肺动脉束带组（PAB） 30只大鼠在出生后6 h内行水平开胸术，肺动脉束带组（PAB） 30只大鼠，假手术组（PA） 30只大鼠不束带。记录小鼠的身体生长和死亡率。出生后第7天超声心动图检查PA收缩（P7）。通过计算机断层扫描和三维重建评估肺形态。采用苏木精和伊红（H&E）染色、马松三色染色、tdt介导的dUTP镍端标记法和CD31标记法观察两组小鼠的组织学差异。PA超证实P7缩窄。与假手术组相比，PAB组新生儿的体格生长、生存分数和肺几何体积随时间的推移而降低（p < 0.05）。PBF减少的组织学表现为肺泡明显简化，PAB组桡骨肺泡计数和肺泡间隔厚度明显降低（p < 0.0001），肺动脉膜层更薄/不均匀，管腔更小。与假手术组相比，PAB组肺泡毛细血管床缺损、肺胶原沉积增强、肺泡上皮细胞凋亡增加（p < 0.0001）。一种新生大鼠PAB模型表明，婴儿期早期PBF减少会损害肺泡化和肺微血管。
The aim of this study was to establish a neonatal rat model of decreased pulmonary blood flow (PBF) for studying pulmonary pathophysiological changes in newborn lung development with reduced PBF. Horizontal thoracotomy surgery with banding of the main pulmonary artery (PA) was performed on 30 rats in the PA banding (PAB) group and without banding on another 30 rats in the sham group within 6 h after birth. The body growth and mortality were recorded. Constriction of PA was checked by echocardiography on postnatal day 7 (P7). Lung morphology was assessed with computed tomography scanning and three-dimensional reconstruction. Histological differences of two groups were evaluated using hematoxylin and eosin (H&E) staining, Masson's trichrome staining, TdT-mediated dUTP nick-end labeling assay, and CD31 labeling with microscopic examination. PA ultrasound confirmed the establishment of constriction on P7. Relative to the sham group, the neonates' physical growth, survival fraction, and lung geometry volume were decreased in the PAB group over time (p < 0.05). Histologic appearance with reduced PBF characterized a markedly simplified alveolarization with noted lower radial alveolar count and alveolar septal thickness in the PAB group (p < 0.0001), pulmonary arteries with thinner/uneven membranous layers and smaller lumina. The deficient alveolar capillary bed, enhanced pulmonary collagen deposition, and increased apoptotic alveolar epithelium were significant in the PAB group compared to the sham group (p < 0.0001). A neonatal rat PAB model demonstrated that PBF reduction during early infancy impairs alveolarization and pulmonary microvasculature.