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首页> 美国卫生研究院文献>Physiological Reports >Mineralocorticoid effects in the late gestation ovine fetal lung
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Mineralocorticoid effects in the late gestation ovine fetal lung

机译：盐皮质激素在妊娠后期胎儿胎肺中的作用

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This study was designed to determine the effects of corticosteroids at MR in the late‐gestation fetal lung. Since both the mineralocorticoid receptor (MR) and the glucocorticoid receptor (GR) are expressed at relatively high levels in the fetal lung, endogenous corticosteroids may act at MR as well as GR in the preterm fetal lung. The GR agonist, betamethasone, the MR agonist, aldosterone, or both were infused intravenously for 48 h in ovine fetuses of approximately 130 days gestation. Effects on airway pressures during stepwise inflation of the in situ lung, expression of ENaC alpha (SCNN1A), ENaC beta (SCNN1B), and Na,K ATPase (ATP1A1), and elastin and collagen content were determined after the infusions. We found that aldosterone significantly reduced the airway pressure measured during the initial step in inflation of the lung, although aldosterone had no overall effect on lung compliance, nor did aldosterone induce expression of ENaCα, ENaCβ or Na,K ATPaseα1. Betamethasone significantly increased expression of the epithelial sodium channel (ENaC) subunit mRNAs, and collagen and elastin content in the lungs, although this dose of betamethasone also had no effect on lung compliance. There was no synergy between effects of the MR and GR agonists. Transcriptomic analysis suggested that although aldosterone did not alter genes in pathways related to epithelial sodium transport, aldosterone did alter genes in pathways involved in cell proliferation in the lungs. The results are consistent with corticosteroid‐induced fluid reabsorption at birth through GR rather than MR, but suggest that MR facilitates lung maturation, and may contribute to inflation with the first breaths via mechanisms distinct from known aldosterone effects in other epithelia.
机译：本研究旨在确定糖皮质激素对妊娠晚期胎儿肺部MR的影响。由于盐皮质激素受体（MR）和糖皮质激素受体（GR）在胎儿肺中均以相对较高的水平表达，因此内源性皮质类固醇可能在早产儿肺中同时作用于MR和GR。将GR激动剂，倍他米松，MR激动剂，醛固酮或两者同时静脉滴注在妊娠约130天的绵羊胎儿中48小时。输注后确定对肺原位逐步充气，ENaCα（SCNN1A），ENaC beta（SCNN1B）和Na，K ATPase（ATP1A1）的表达以及弹性蛋白和胶原蛋白含量对气道压力的影响。我们发现，尽管醛固酮对肺顺应性没有总体影响，但醛固酮也没有诱导ENaCα，ENaCβ或Na，KATPaseα1的表达，但醛固酮显着降低了肺膨胀初期的气道压力。倍他米松显着增加了肺中上皮钠通道（ENaC）亚基的表达以及胶原和弹性蛋白含量，尽管倍他米松的剂量也对肺顺应性没有影响。 MR和GR激动剂之间没有协同作用。转录组学分析表明，尽管醛固酮并未改变上皮钠转运相关通路中的基因，但醛固酮确实改变了与肺细胞增殖有关的通路中的基因。该结果与出生时皮质激素通过GR而不是MR重吸收液体相一致，但表明MR促进了肺成熟，并可能通过不同于其他上皮中已知的醛固酮作用的机制促成首次呼吸时的通气。

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