Administration of antenatal glucocorticoids and postnatal surfactant ameliorates respiratory distress syndrome-associated neonatal lethality in Erk3(-/-) mouse pups.
Administration of antenatal glucocorticoids and postnatal surfactant ameliorates respiratory distress syndrome-associated neonatal lethality in Erk3(-/-) mouse pups.
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DOI：
10.1038/pr.2014.54
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发表时间：
2014-07
影响因子：
3.6
通讯作者：
Aagaard, Kjersti
中科院分区：
文献类型：
--
作者：
Guaman, Milenka Cuevas;Sbrana, Elena;Shope, Cynthia;Showalter, Lori;Hu, Min;Meloche, Sylvain;Aagaard, Kjersti
呼吸窘迫综合征（RDS）仍然是婴儿发病和死亡的普遍原因。我们之前已经证明，Erk3 的缺失会导致肺不成熟和新生儿死亡。使用 RNA-Seq，我们确定促肾上腺皮质激素释放激素 (CRH) 和表面活性蛋白 B (SFTPB) 是 Erk3 依赖性肺成熟的潜在分子介质。在这项研究中，我们描述了产前糖皮质激素和产后表面活性剂对 Erk3 缺失小鼠的新生儿存活率的影响。在双交叉设计中，我们在肺部发育的囊状阶段给怀孕母鼠注射地塞米松（dex）或盐水，然后通过吸入插管注射出生后表面活性剂或盐水。记录存活率，进行详细的肺组织学分析以及 CRH 和 SFTPB 蛋白表达的染色。如果不进行治疗，Erk3 缺失的幼崽会在出生后 6 小时内死亡，并伴有通气空间减少、肺泡间隔变薄受损以及 PAS 阳性糖原储存丰富；如人类 RDS 中所述。 dex和表面活性剂的施用改善了Erk3−/−幼仔的RDS相关致死率，并通过加速肺CRH的下调和部分挽救SFTPB的产生来部分恢复功能性胎肺成熟。这些发现强调 Erk3 对于 II 型细胞的终末分化、SFTPB 产生和胎儿肺成熟是不可或缺的。
Respiratory distress syndrome (RDS) persists as a prevalent cause of infant morbidity and mortality. We have previously demonstrated that deletion of Erk3 results in pulmonary immaturity and neonatal lethality. Using RNA-Seq, we identified corticotrophin releasing hormone (CRH) and surfactant protein B (SFTPB) as potential molecular mediators of Erk3-dependent lung maturation. In this study, we characterized the impact of antenatal glucocorticoids and postnatal surfactant on neonatal survival of Erk3 null mice. In a double crossover design, we administered dexamethasone (dex) or saline to pregnant dams during the saccular stage of lung development, followed by postnatal surfactant or saline via inhalation intubation. Survival was recorded, detailed lung histological analysis and staining for CRH and SFTPB protein expression was performed. Without treatment, Erk3 null pups die within 6 hours of birth with reduced aerated space, impaired thinning of the alveolar septa, and abundant PAS-positive glycogen stores; as described in human RDS. The administration of dex and surfactant improved RDS-associated lethality of Erk3−/− pups, and partially restored functional fetal lung maturation by accelerating the down-regulation of pulmonary CRH and partially rescuing production of SFTPB. These findings emphasize that Erk3 is integral to terminal differentiation of type II cells, SFTPB production, and fetal pulmonary maturity.
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DOI：
10.1152/ajplung.2001.280.4.l689
发表时间：
2001-04-01
影响因子：
4.9
作者：
Kramer, BW;Jobe, AH;Ikegami, M
通讯作者：
Ikegami, M
影响因子：
3.7
作者：
Fukushi, Masaya;Yamashita, Makoto;Kudo, Koichiro
通讯作者：
Kudo, Koichiro
影响因子：
64.8
作者：
MUGLIA, L;JACOBSON, L;MAJZOUB, JA
通讯作者：
MAJZOUB, JA
DOI：
10.1053/siny.2001.0068
发表时间：
2001-08-01
期刊：
Seminars in neonatology : SN
影响因子：
--
作者：
Jobe, A H
通讯作者：
Jobe, A H
DOI：
10.1016/s0002-9378(88)80163-7
发表时间：
1988-10-01
影响因子：
9.8
作者：
LAATIKAINEN, TJ;RAISANEN, IJ;SALMINEN, KR
通讯作者：
SALMINEN, KR