All-trans retinoic acid and intra-amniotic endotoxin-mediated effects on fetal sheep lung.
All-trans retinoic acid and intra-amniotic endotoxin-mediated effects on fetal sheep lung.
复制标题
全反式视黄酸和羊膜内内毒素介导的对胎羊肺的影响。
DOI：
10.1002/ar.20743
复制
发表时间：
2008
期刊：
影响因子：
--
通讯作者：
Jobe,AH
中科院分区：
文献类型：
--
作者：
Kramer,BW;Albertine,KH;Moss,TJM;Nitsos,I;Ladenburger,A;Speer,CP;Newnham,JP;Jobe,AH
全反式维甲酸(RA)是一种强有力的肺发育调节剂。绒毛膜羊膜炎经常与早产有关，会导致胎儿肺部炎症，改善肺功能，但也会导致肺泡简化和微血管损伤。内毒素介导的绒毛膜羊膜炎使胎肺中RA浓度降低到对照组的16%。我们假设在绒毛膜羊膜炎诱导前给胎儿注射维甲酸可以保留远端空气空间的分隔。在妊娠124天和胎儿治疗后7天，在羊膜内注射内毒素(20 mg，E.Coli055：B5)或生理盐水前3小时，配对的单胎母羊被分配到接受2000IU的RA橄榄油(或仅橄榄油)中的胎儿肌肉治疗。对右侧颅叶进行形态计量学分析。RA治疗不影响绒毛膜羊膜炎引起的胎儿和全身炎症，也不影响肺组织中IL-8的浓度。RA单独给药不会改变肺结构。与对照组(5±3mL/kg)相比，内毒素(22±4mL/kg)或RA+内毒素(20±3mL/kg；P<；0.05)组肺体积增加相似。内毒素性绒毛膜羊膜炎后肺泡壁厚度为4.2±0.3μm，对照组为6.0±0.4μm(P<0.0 5)，RA+内毒素组为5.5±0.2μm(P<；0.0 5 vs对照组，P<0.0 5)。对抗内毒素)。内毒素性绒毛膜羊膜炎的腔隙与组织的比值为4.6±0.3，对照组为2.1±0.3，RA+内毒素组为4.1±0.5。我们的结论是，用RA治疗胎儿并不能阻止炎症诱导的肺泡简化。Anat Rec，2008。©2008 Wiley-Liss，Inc.
All‐trans retinoic acid (RA) is a potent modulator of lung development. Chorioamnionitis, which is frequently associated with preterm birth, causes fetal lung inflammation and improves lung function but also results in alveolar simplification and microvascular injury. Endotoxin‐mediated chorioamnionitis reduces RA concentration in the fetal lung to 16% of control values. We hypothesized that administration of RA to the fetus before induction of chorioamnionitis would preserve septation of the distal airspaces. Time‐mated ewes with singletons were assigned to receive a fetal intramuscular treatment with 20,000 IU of RA in olive oil (or olive oil only) 3 hr prior to intra‐amniotic injection of endotoxin (20 mg, E. coli 055:B5) or saline, at 124‐day gestational age and 7 days after the fetal treatment. The right cranial lung lobe was processed for morphometric analysis. RA treatment did not affect chorioamnionitis‐induced fetal and systemic inflammation or interleukin‐8 concentrations in lung tissue. RA administration alone did not alter lung structure. Relative to control lungs (5 ± 3 mL/kg), lung volume increased similarly with endotoxin (22 ± 4 mL/kg) or RA plus endotoxin (20 ± 3 mL/kg;P< 0.05). Alveolar wall thickness was 4.2 ± 0.3 μm after endotoxin‐induced chorioamnionitis, 6.0 ± 0.4 μm in controls (P< 0.05 versus endotoxin) and 5.5 ± 0.2 μm after RA and endotoxin (P< 0.05 versus control, n.s. versus endotoxin). The ratio of airspace versus tissue was 4.6 ± 0.3 in endotoxin‐induced chorioamnionitis, 2.1 ± 0.3 in controls and 4.1 ± 0.5 after RA and endotoxin. We conclude that fetal treatment with RA did not prevent inflammation‐induced alveolar simplification. Anat Rec, 2008. © 2008 Wiley‐Liss, Inc.