Effect of betamethasone administration to the pregnant baboon at 0.75 gestation on placental eNOS distribution and activity

Effect of betamethasone administration to the pregnant baboon at 0.75 gestation on placental eNOS distribution and activity
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DOI:
10.1016/j.placenta.2004.03.005
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发表时间:
2004-11-01
期刊:
影响因子:
3.8
通讯作者:
Nathanielsz, PW
Nathanielsz, PW
中科院分区:
医学3区
文献类型:
--
作者:
Aida, K;Wang, XL;Nathanielsz, PW

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倍他米松经常用于有早产风险的孕妇,以加速胎儿肺成熟。母亲服用倍他米松会显著改变胎儿的外周血管,升高胎儿血压,并导致胎儿生长受限。内皮型一氧化氮合酶(ENOS)在调节血管张力中起重要作用。我们推测倍他米松对胎儿血管的影响包括eNOS活性降低。我们用ELISA法(倍他米松处理组与对照组相比,0.48+/-0.28vs1.57+/-0.45,p<0.05)和免疫组织化学方法检测到合体滋养层细胞和血管内皮细胞中胎盘eNOS总蛋白的显著降低。倍他米松暴露后,eNOS mRNA和酶活性呈下降趋势,但差异无统计学意义。在有女性胎儿存在的情况下,对照组和倍他米松处理组的狒狒胎盘中eNOS蛋白的表达均高于男性胎儿。倍他米松组对enos基因表达的影响与胎儿性别相同。总之,母亲服用倍他米松后胎盘eNOS功能的多项指标持续下降,这可能在妊娠晚期服用倍他米松引起的心血管动力学改变和胎儿生长迟缓中起一定作用。(C)2004爱思唯尔有限公司。保留所有权利。
Betamethasone is frequently administered to pregnant women at risk of premature labor to accelerate fetal lung maturation. Maternally administered betamethasone produces pronounced changes in the fetal peripheral vasculature, raises fetal blood pressure and produces fetal growth restriction. Endothelial nitric oxide synthase (eNOS) plays an important role in regulating vascular tone. We hypothesized that effects of betamethasone on the fetal vasculature include decreased eNOS activity. We determined a significant depression of total placental eNOS protein measured by ELISA (betamethasone treated vs control, 0.48 +/- 0.28 vs 1.57 +/- 0.45, p < 0.05) and immunohistochemistry in both syncytiotrophoblast and vascular endothelium. Following betamethasone exposure, eNOS mRNA and enzyme activity showed decreasing trends which were not statistically significant. eNOS protein was higher in the placentas of both control and betamethasone treated baboons in the presence of a female fetus compared with a male fetus. The same effect of the sex of the fetus was observed in the betamethasone group for eNOS mRNA. In conclusion, maternally administered betamethasone produces a consistent decrease in several indices of placental eNOS function that may play a role in the altered cardiovascular dynamics and fetal growth retardation produced by betamethasone administration in late pregnancy. (C) 2004 Elsevier Ltd. All rights reserved.