Endothelin receptor expression in human lungs of newborns with congenital diaphragmatic hernia
Endothelin receptor expression in human lungs of newborns with congenital diaphragmatic hernia
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DOI：
10.1002/path.1677
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发表时间：
2005-01-01
影响因子：
7.3
通讯作者：
Berrebi, D
中科院分区：
文献类型：
--
作者：
de Lagausie, P;de Buys-Roessingh, A;Berrebi, D
先天性肺动脉疝（CDH）是新生儿期难治性呼吸衰竭的主要原因，其特征是新生儿持续性肺动脉高压（PPHN）和肺发育不全。内皮素-1（ET-1）的失调在PPHN的病理生理过程中起重要作用，ET-1通过与A型（ETA）和B型（ET B）受体结合发挥作用。本研究采用免疫组织化学方法检测了10例CDH新生儿肺组织和4例正常新生儿肺组织中ETA和ETB受体蛋白的表达，以探讨ETA和ETB表达失调是否与PPHN的发生有关。然后在激光显微切割的肺阻力动脉中使用实时RT-PCR定量ETA和ETB mRNA。在新生儿CDH的肺中，ETA和ETB受体的免疫组化显示在增厚的肺动脉中膜过度表达。使用激光显微切割和实时RT-PCR，较高水平的ETA和ETB的mRNA被发现在CDH肺动脉比对照组：这种增加是更明显的ETA mRNA。这项研究首次证明了患有CDH和PPHN的新生儿中ET-1受体失调与肺动脉结构改变相关。这种失调优先影响ETA受体。这些结果表明，ET-1受体的失调可能有助于PPHN与CDH。版权所有（C）2004大不列颠和爱尔兰病理学会。出版社：John Wiley Sons，Ltd
Congenital diaphragmatic hernia (CDH) is a major cause of refractory respiratory failure in the neonatal period and is characterized by persistent pulmonary hypertension of the newborn (PPHN) and pulmonary hypoplasia. Endothelin-1 (ET-1) dysregulation may play a significant role in the pathophysiology of PPHN and ET-1 acts through binding to type A (ETA) and type B (ETB) receptors. Therefore, ETA and ETB receptor protein expression was studied using immunohistochemistry in 10 lung specimens obtained from newborns with CDH, and 4 normal lung specimens, in order to explore whether dysregulation of ETA and ETB expression contributes to PPHN. ETA and ETB mRNAs were then quantified using real-time RT-PCR in laser-microdissected pulmonary resistive arteries. In the lungs of newborns with CDH, immunohistochemistry of both ETA and ETB receptors demonstrated over-expression in the thickened media of pulmonary arteries. Using laser microdissection and real-time RT-PCR, higher levels of ETA and ETB mRNA were found in CDH pulmonary arteries than in controls: this increase was more pronounced for ETA mRNA. This study provides the first demonstration of ET-1 receptor dysregulation in association with structural alteration of pulmonary arteries in newborns with CDH and PPHN. This dysregulation preferentially affects the ETA receptor. These results suggest that dysregulation of ET-1 receptors may contribute to PPHN associated with CDH. Copyright (C) 2004 Pathological Society of Great Britain and Ireland. Published by John Wiley Sons, Ltd.