Antounians Lina, Figueira Rebeca Lopes, Sbragia Lourenço, Zani Augusto
Division of General and Thoracic Surgery, The Hospital for Sick Children, Toronto, Ontario, Canada.
Developmental and Stem Cell Biology Program, Peter Gilgan Centre for Research and Learning, The Hospital for Sick Children, Toronto, Ontario, Canada.
Eur J Pediatr Surg. 2019 Aug;29(4):317-327. doi: 10.1055/s-0039-1693993. Epub 2019 Jul 31.
Congenital diaphragmatic hernia (CDH) is a devastating disease that still carries a high mortality and morbidity rate. Poor outcomes for fetuses and infants with CDH are mainly related to pulmonary hypoplasia (PH) and pulmonary vascular remodeling that leads to pulmonary hypertension (PHTN). Over the last five decades, research efforts have focused on modeling CDH not only to study the pathophysiology of the diaphragmatic defect, pulmonary hypoplasia, and pulmonary hypertension, but also to identify therapies that would promote lung growth and maturation, and correct vascular remodeling. As CDH is a multifactorial condition whose etiology remains unknown, there is not a single model of CDH, rather several ones that replicate different aspects of this disease. While small animals like the mouse and the rat have mainly been used to uncover biological pathways underlying the diaphragmatic defect and poor lung growth, larger animals like the lamb and the rabbit models have been instrumental for pursuing medical and surgical interventions. Overall, the use of animal models has indeed advanced our knowledge on CDH and helped us test innovative therapeutic options. For example, the lamb model of CDH has been the paradigm for testing fetal surgical procedures, including tracheal occlusion, which has been translated to clinical use. In this review, we outline the induction protocols of CDH in animals with the use of chemicals, dietary changes, genetic alterations, and surgical maneuvers, and we describe the studies that have translated experimental results to the bedside.
先天性膈疝（CDH）是一种严重的疾病，其死亡率和发病率仍然很高。患有CDH的胎儿和婴儿预后不良主要与肺发育不全（PH）和导致肺动脉高压（PHTN）的肺血管重塑有关。在过去的五十年里，研究工作集中在建立CDH模型，不仅用于研究膈肌缺损、肺发育不全和肺动脉高压的病理生理学，还用于确定能够促进肺生长和成熟以及纠正血管重塑的治疗方法。由于CDH是一种病因不明的多因素疾病，不存在单一的CDH模型，而是有几种模型可以复制该疾病的不同方面。虽然小鼠和大鼠等小动物主要用于揭示膈肌缺损和肺生长不良背后的生物学途径，但羔羊和兔模型等较大动物对于探索医学和外科干预措施起到了重要作用。总体而言，动物模型的使用确实增进了我们对CDH的了解，并帮助我们测试创新的治疗方案。例如，CDH的羔羊模型一直是测试包括气管闭塞在内的胎儿手术程序的范例，该程序已转化为临床应用。在这篇综述中，我们概述了使用化学物质、饮食改变、基因改变和手术操作在动物中诱导CDH的方案，并描述了将实验结果转化为临床应用的研究。
