Effect of temporary tracheal occlusion on the endothelin system in experimental cases of diaphragmatic hernia

Effect of temporary tracheal occlusion on the endothelin system in experimental cases of diaphragmatic hernia
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DOI:
10.1080/019021490927079
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发表时间:
2005-05-01
影响因子:
1.7
通讯作者:
Laberge, JM
Laberge, JM
中科院分区:
医学4区
文献类型:
--
作者:
Cloutier, M;Seaborn, T;Laberge, JM

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之前,作者已经表明,气管闭塞(TO)部分逆转了先天性疝(CDH)诱导的肺动脉高压(PH)和异常肺血管发育的发作,而闭塞(TR)的释放则消除了这些临床获益。由于它们的促有丝分裂和血管活性特性,作者假设CDH羔羊肺中内皮素(ET)-1和ET受体(ETA)基因的表达增加,并且这种增加在CDH + TO中部分消除,但在CDH + TO中没有。+ TR。在妊娠80天(gd)时,在胎羊中创建手术左侧CDH,然后在108 gd时创建TO,并在129 gd时创建TR。比较了四组:CDH、CDH + TO、CDH + TO + TR和未手术对照组(C)。北方杂交检测CDH组ET-1和ETA水平明显低于CDH + TO +/- TR组(P <0.05)。除内皮细胞外,CDH +/- TO +/- TR组的气道和血管内皮素蛋白表达水平低于对照组(P <0.05)。相反,与对照组相比,CDH +/- TO +/- TR组气道和血管平滑肌的ETA蛋白表达水平更高(P <0.05)。这些结果表明,内皮素系统参与的肺动脉高压与CDH是有限的。然而,内皮素系统似乎是调制过程中的发展。
Previously, the authors have shown that tracheal occlusion ( TO) partially reverses the onset of congenital diaphragmatic hernia (CDH)-induced pulmonary hypertension (PH) and abnormal pulmonary vascular development whereas release of the occlusion (TR) abolishes these clinical benefits. As a consequence of their mitogenic and vasoactive properties, the authors hypothesize that the expression of endothelin (ET)-1 and ET receptor (ETA) genes is increased in lungs of CDH lambs, and that this increase is abolished partially in CDH + TO but not in CDH + TO + TR. A surgical left-sided CDH was created in fetal lambs at 80 days of gestation (gd), followed by TO at 108 gd, and by TR at 129 gd. Four groups were compared: CDH, CDH + TO, CDH + TO + TR, and nonoperated controls ( C). Assessment of mRNA expression by Northern blot showed significantly lower ET-1 and ETA levels in the CDH group than in the CDH + TO +/- TR groups ( P < .05). Endothelin protein expression levels were lower in CDH +/- TO +/- TR groups when compared with controls for airways and vessels ( P < .05) with the exception of endothelial cells. In contrast, ETA protein expression levels were higher in CDH +/- TO +/- TR groups compared with controls for airways and blood vessels smooth muscles ( P < .05). These results suggest that involvement of the endothelin system in the pulmonary hypertension associated with CDH is limited. However, the endothelin system appears to be modulated during development.