Leptin Matures Aspects of Lung Structure and Function in the Ovine Fetus.
Leptin Matures Aspects of Lung Structure and Function in the Ovine Fetus.
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DOI：
10.1210/en.2015-1729
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发表时间：
2016-01
期刊：
影响因子：
4.8
通讯作者：
Forhead AJ
中科院分区：
文献类型：
--
作者：
De Blasio MJ;Boije M;Kempster SL;Smith GC;Charnock-Jones DS;Denyer A;Hughes A;Wooding FB;Blache D;Fowden AL;Forhead AJ
在人类和绵羊胎儿中，糖皮质激素刺激瘦素分泌，尽管瘦素在多大程度上介导糖皮质激素对肺发育的成熟作用尚不清楚。本研究探讨了出生前给予瘦素对肺结构和功能指标的影响。长期插管的单胎羊胎儿从妊娠125天（足月~ 145天）起静脉输注生理盐水或重组羊瘦素（0.5 mg/kg · d瘦素（LEP），0.5 LEP或1.0 mg/kg · d，1.0 LEP），连续5天。在输注过程中，瘦素给药增加了血浆瘦素浓度，但不增加皮质醇浓度。在输注的第五天，0.5 LEP降低肺泡壁厚度，增加压力-容积收缩曲线的闭合压力时的容积、肺泡间隔弹性蛋白含量、次级间隔嵴密度以及瘦素受体（Ob-R）和表面活性蛋白（SP）B的mRNA丰度。两种治疗均不影响静态肺顺应性、40 cmH 2 O时的最大肺容积、肺室容积、肺泡表面积、肺糖原、长型信号传导分子Ob-Rb或磷酸化信号转导子和转录激活子-3的蛋白含量，或SP-A、C或D、弹性蛋白、血管内皮生长因子-A、血管内皮生长因子受体2、血管紧张素转换酶、过氧化物酶体增殖物激活受体γ或甲状旁腺相关肽。妊娠晚期绵羊胎儿给予瘦素可促进肺成熟，包括SP-B的上调。
In human and ovine fetuses, glucocorticoids stimulate leptin secretion, although the extent to which leptin mediates the maturational effects of glucocorticoids on pulmonary development is unclear. This study investigated the effects of leptin administration on indices of lung structure and function before birth. Chronically catheterized singleton sheep fetuses were infused iv for 5 days with either saline or recombinant ovine leptin (0.5 mg/kg · d leptin (LEP), 0.5 LEP or 1.0 mg/kg · d, 1.0 LEP) from 125 days of gestation (term ∼145 d). Over the infusion, leptin administration increased plasma leptin, but not cortisol, concentrations. On the fifth day of infusion, 0.5 LEP reduced alveolar wall thickness and increased the volume at closing pressure of the pressure-volume deflation curve, interalveolar septal elastin content, secondary septal crest density, and the mRNA abundance of the leptin receptor (Ob-R) and surfactant protein (SP) B. Neither treatment influenced static lung compliance, maximal lung volume at 40 cmH2O, lung compartment volumes, alveolar surface area, pulmonary glycogen, protein content of the long form signaling Ob-Rb or phosphorylated signal transducers and activators of transcription-3, or mRNA levels of SP-A, C, or D, elastin, vascular endothelial growth factor-A, the vascular endothelial growth factor receptor 2, angiotensin-converting enzyme, peroxisome proliferator-activated receptor γ, or parathyroid hormone-related peptide. Leptin administration in the ovine fetus during late gestation promotes aspects of lung maturation, including up-regulation of SP-B.