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母体视黄酸给药对羊水过少暴露胎儿肺血管生成的影响。

Effects of maternal retinoic acid administration on lung angiogenesis in oligohydramnios-exposed fetal rats.

机构信息

Department of Pediatrics, Taipei Medical University Hospital, Taipei, Taiwan.

出版信息

Pediatr Neonatol. 2013 Apr;54(2):88-94. doi: 10.1016/j.pedneo.2012.11.009. Epub 2013 Jan 11.

Abstract

BACKGROUND

All-trans retinoic acid (ATRA) induces in vitro angiogenesis and vascular endothelial growth factor (VEGF) secretion. Prenatal administration of vitamin A tends to increase the pulmonary and plasma levels of VEGF in the developing mouse. The aims of this study were to examine the effects of maternal retinoic acid treatment on lung VEGF expression and angiogenesis in oligohydramnios-exposed fetal rats.

METHODS

On day 16 of gestation, pregnant Sprague-Dawley rats were randomly assigned to either the retinoic acid group (intragastric ATRA at 10 mg/kg body weight) or the vehicle group. We punctured each uterine sac to produce oligohydramnios, and fetuses in the opposite uterine horn served as controls. On day 21 of gestation, the fetuses were delivered by cesarean section.

RESULTS

Rats exposed to oligohydramnios exhibited lower lung weights and lung/body weight ratios, and ATRA exhibited no effects on the body or lung weights of oligohydramnios-exposed rats. Lung microvessel density decreased in oligohydramnios-exposed rats of maternal vehicle-treated dams. Microvessel density was comparable between the oligohydramnios + retinoic acid group and the control + retinoic acid group. VEGF expression was comparable among control and oligohydramnios-exposed rats of maternal vehicle- or retinoic acid-treated dams.

CONCLUSION

Maternal retinoic acid treatment did not increase lung VEGF expression or enhance lung development in oligohydramnios-exposed fetal rats. These results do not support the use of maternal retinoic acid to prevent oligohydramnios-induced pulmonary hypoplasia in the pseudoglandular stage.

摘要

背景

全反式视黄酸(ATRA)可诱导体外血管生成和血管内皮生长因子(VEGF)分泌。产前给予维生素 A 会增加发育中小鼠肺和血浆中的 VEGF 水平。本研究旨在探讨母体视黄酸处理对羊水过少暴露胎儿大鼠肺 VEGF 表达和血管生成的影响。

方法

在妊娠第 16 天,将怀孕的 Sprague-Dawley 大鼠随机分为视黄酸组(胃内 ATRA 10mg/kg 体重)或载体组。我们刺破每个子宫囊以产生羊水过少,并将对侧子宫角中的胎儿作为对照。在妊娠第 21 天,通过剖腹产分娩胎儿。

结果

羊水过少暴露的大鼠肺重和肺/体重比降低,ATRA 对羊水过少暴露大鼠的体重或肺重没有影响。羊水过少暴露的母体载体处理的大鼠肺微血管密度降低。羊水过少+视黄酸组和对照+视黄酸组之间的微血管密度相当。VEGF 表达在母体载体或视黄酸处理的对照和羊水过少暴露的大鼠之间相当。

结论

母体视黄酸处理不会增加羊水过少暴露胎儿大鼠的肺 VEGF 表达或增强肺发育。这些结果不支持在假腺期使用母体视黄酸预防羊水过少引起的肺发育不良。

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