日本小児循環器学会雑誌 Pediatric Cardiology and Cardiac Surgery

Online ISSN: 2187-2988 Print ISSN: 0911-1794
特定非営利活動法人日本小児循環器学会 Japanese Society of Pediatric Cardiology and Cardiac Surgery
〒162-0801東京都新宿区山吹町358-5アカデミーセンター Japanese Society of Pediatric Cardiology and Cardiac Surgery Academy Center, 358-5 Yamabuki-cho, Shinju-ku, Tokyo 162-0801, Japan
Pediatric Cardiology and Cardiac Surgery 35(2): 99-111 (2019)
doi:10.9794/jspccs.35.99

ReviewReview

小児肺高血圧に関連の深い実験モデル肺動脈性肺高血圧・気管支肺異形成・先天性横隔膜ヘルニアPediatric Pulmonary Hypertension and Relevant Experimental Animal Models: Pulmonary Arterial Hypertension, Bronchopulmonary Dysplasia and Congenital Diaphragmatic Hernia

三重大学医学部医学系研究科麻酔集中治療学・小児科学Department of Anesthesiology and Critical Care Medicine and Pediatrics, Mie University ◇ Mie, Japan

発行日:2019年5月1日Published: May 1, 2019
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小児肺高血圧(PH)が,特発性・遺伝性以外に,心疾患,呼吸疾患,肝門脈疾患や全身疾患など多彩な病態を基礎として発症することは成人と同様であるが,小児の特徴として,肺の発生・発達・成長の影響を大きく受けることは重要である.気管支肺異形成(BPD)や先天性横隔膜ヘルニア(CDH)など,周産期の適応障害や肺の発達成長障害の重要性が強調された小児PHの臨床分類も考案されている.PHの血管病変形成に関する研究は,肺動脈性肺高血圧に見られる血管病変,血管機能変化や遺伝子異常を中心に進められ,実験動物では,モノクロタリン投与ラット,慢性低酸素暴露,SU5416+慢性低酸素暴露やBMPR2などの遺伝子改変モデルが用いられている.肺発達成長障害に関しては,高濃度酸素投与,人工呼吸器による圧伸展,出生前の炎症などのBPDモデル,nitorofen投与,胎児手術でのCDH作成,横隔膜欠損をきたす遺伝子改変などのCDHモデルからも,新たな知見が得られている.

Pulmonary hypertension (PH) causes significant morbidity and mortality in diverse childhood diseases. As in adult PH, pediatric PH may be a result of heart disease, respiratory disease, hepatic portal vein disease, systemic diseases as well as idiopathic or heritable forms. However, the main characteristic of pediatric PH that distinguishes it from adult PH is its association with lung development and growth. This includes prenatal and early postnatal factors as bronchopulmonary dysplasia (BPD) and congenital diaphragmatic hernia (CDH). A number of animal models have been developed and refined to demonstrate the pathological pulmonary hallmarks found in lungs from patients with pulmonary arterial hypertension (PAH), BPD, and CDH.

Although monocrotaline and chronic hypoxia models are long-established and commonly used models of PAH, the Sugen/hypoxia model, which demonstrates human PAH pathology quite well, has been widely used as a model of PAH. In modeling BPD in experimental animals, a variety of stimuli such as hyperoxia, alveolar stretch by mechanical ventilation and antenatal inflammation have been applied in rodents and larger animals. Nitorofen, a teratogen, has commonly been used to cause CDH in animals. Recently, genetic models of CDH have become available, and multiple genetic models have CDH associated with them as part of their phenotype.

Investigations using these animal models have resulted in the discovery of many important genetic and molecular contributors to PH pathogenesis. In this review, commonly used and newly devised animal models of PH are discussed to highlight the effect of basic research on clinical practice in pediatric PH.

Key words: pulmonary hypertension; animal model; bronchopulmonary dysplasia; congenital diaphragmatic hernia

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This page was last modified on 2019-05-17T19:22:39.000+09:00


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