Dose-dependent effects of glucocorticoids on pulmonary vascular development in a murine model of hyperoxic lung injury.
Dose-dependent effects of glucocorticoids on pulmonary vascular development in a murine model of hyperoxic lung injury.
复制标题
DOI：
10.1038/pr.2016.1
复制
发表时间：
2016-05
影响因子：
3.6
通讯作者：
Farrow KN
中科院分区：
文献类型：
--
作者：
Perez M;Wisniewska K;Lee KJ;Cardona HJ;Taylor JM;Farrow KN
新生小鼠暴露于高氧导致肺血管重塑和异常磷酸二酯酶-5（PDE5）信号传导。虽然糖皮质激素经常用于新生儿重症监护病房，但其对发育中的肺血管和PDE 5的影响知之甚少。我们试图确定氢化可的松（HC）对新生小鼠高氧肺损伤模型肺血管发育和PDE5的影响。C57 BL/6小鼠在出生后24小时内置于21% O2或75% O2中，并接受HC（1、5或10 mg/kg，每隔一天皮下注射一次）或溶剂。在14天时，评估右心室肥大（RVH）、中壁厚度（MWT）、肺形态学和肺动脉（PA）PDE 5活性。在暴露于21%或95% O2 ± 100 nM HC 24 h的分离的肺动脉平滑肌细胞（PASMC）中测量PDE 5活性。高氧导致肺泡简化、RVH、MWT增加和PA PDE 5活性增加。HC降低高氧诱导的RVH和衰减MWT。HC对肺泡简化具有剂量依赖性影响。HC降低体内和体外高氧诱导的PDE 5活性。HC可减少高氧诱导的肺血管重塑并减弱PDE 5活性。这些结果表明，HC可以防止高氧损伤的发展中的肺血管。
Exposure of neonatal mice to hyperoxia results in pulmonary vascular remodeling and aberrant phosphodiesterase-5 (PDE5) signaling. Although glucocorticoids are frequently utilized in the NICU, little is known about their effects on the developing pulmonary vasculature and on PDE5. We sought to determine the effects of hydrocortisone (HC) on pulmonary vascular development and on PDE5 in a neonatal mouse model of hyperoxic lung injury. C57BL/6 mice were placed in 21% O2 or 75% O2 within 24h of birth and received HC (1, 5, or 10 mg/kg subcutaneously every other day) or vehicle. At 14d, right ventricular hypertrophy (RVH), medial wall thickness (MWT), lung morphometry, and pulmonary artery (PA) PDE5 activity were assessed. PDE5 activity was measured in isolated pulmonary artery smooth muscle cells (PASMC) exposed to 21% or 95% O2 ± 100nM HC for 24h. Hyperoxia resulted in alveolar simplification, RVH, increased MWT, and increased PA PDE5 activity. HC decreased hyperoxia-induced RVH and attenuated MWT. HC had dose-dependent effects on alveolar simplification. HC decreased hyperoxia-induced PDE5 activity in vivo and in vitro. HC decreases hyperoxia-induced pulmonary vascular remodeling and attenuates PDE5 activity. These findings suggest that HC may protect against hyperoxic injury in the developing pulmonary vasculature.