Animal Models, Learning Lessons to Prevent and Treat Neonatal Chronic Lung Disease.
Animal Models, Learning Lessons to Prevent and Treat Neonatal Chronic Lung Disease.
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DOI：
10.3389/fmed.2015.00049
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发表时间：
2015
影响因子：
3.9
通讯作者：
Jobe AH
中科院分区：
文献类型：
--
作者：
Jobe AH
支气管肺发育不良（BPD）是一种独特的损伤综合征，由未成熟和发育中的肺长期损伤和修复引起。BPD的分隔减少和微血管发育减少的表型可以在新生啮齿动物中复制，增加慢性氧暴露，以及在早产灵长类动物和绵羊中使用氧气和/或机械通气。氧化剂、炎性激动剂和/或机械通气牵张损伤引起的炎症似乎促进了解剖异常。针对特定炎症细胞或通路或针对减少通气介导的损伤的多种干预措施可以基本上预防与足月啮齿动物和早产绵羊或灵长类动物模型中的BPD相关的解剖学变化。大多数在动物模型中获益的抗炎疗法尚未进行临床测试。经过临床测试的干预措施都没有动物模型预期的那么有效。这些反应的不一致性可能是由发育中动物相对于极早产人类的肺部暴露的产前差异解释的。这些动物通常具有正常的肺，而早产儿的肺暴露于宫内炎症、生长异常、产前皮质类固醇以及对早产原因的影响知之甚少。动物模型对于定义可导致BPD表型的介质至关重要。这些模型对于开发和测试未来有针对性的干预措施以预防和治疗BPD是必要的。
Bronchopulmonary dysplasia (BPD) is a unique injury syndrome caused by prolonged injury and repair imposed on an immature and developing lung. The decreased septation and decreased microvascular development phenotype of BPD can be reproduced in newborn rodents with increased chronic oxygen exposure and in premature primates and sheep with oxygen and/or mechanical ventilation. The inflammation caused by oxidants, inflammatory agonists, and/or stretch injury from mechanical ventilation seems to promote the anatomic abnormalities. Multiple interventions targeted to specific inflammatory cells or pathways or targeted to decreasing ventilation-mediated injury can substantially prevent the anatomic changes associated with BPD in term rodents and in preterm sheep or primate models. Most of the anti-inflammatory therapies with benefit in animal models have not been tested clinically. None of the interventions that have been tested clinically are as effective as anticipated from the animal models. These inconsistencies in responses likely are explained by the antenatal differences in lung exposures of the developing animals relative to very preterm humans. The animals generally have normal lungs while the lungs of preterm infants are exposed variably to intrauterine inflammation, growth abnormalities, antenatal corticosteroids, and poorly understood effects from the causes of preterm delivery. The animal models have been essential for the definition of the mediators that can cause a BPD phenotype. These models will be necessary to develop and test future-targeted interventions to prevent and treat BPD.