Cloprostenol, a prostaglandin F2α analog, induces hypoxia in rat placenta:: BOLD contrast MRI
Cloprostenol, a prostaglandin F2α analog, induces hypoxia in rat placenta:: BOLD contrast MRI
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DOI：
10.1002/nbm.1087
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发表时间：
2007-02-01
影响因子：
2.9
通讯作者：
Dekel, Nava
中科院分区：
文献类型：
--
作者：
Girsh, Eliezer;Plaks, Vicki;Dekel, Nava
在大鼠胚胎-胎盘单位（EPU）中，使用血氧水平依赖性（BOLD）对比监测氯前列醇（一种前列腺素F-2 α（PGF（2 α））类似物）诱导的缺氧。研究表明，在妊娠中期（第16天）给予氯前列醇（0.025 mg/大鼠）可降低EPU氧合，如BOLD对比MRI所示，与相应胎盘中血管内皮生长因子（VEGF）基因（Vegfa）表达的诱导相关（r = 0.56，p = 0.03）。在妊娠早期（第9天），在形成胎盘（p = 0.04）和子宫（p = 0.03）中也观察到对氯前列醇治疗的响应的VEGF mRNA表达升高。氯前列醇增加了形成中胎盘中内皮素-1（ET-1）基因（Edn 1）（p = 0.03）及其相应肽（p = 0.02）的表达水平，以及形成中胎盘（p = 0.009）和子宫（p = 0.01）中内皮素受体A型（ETA）基因（Ednra）的表达。内皮素受体B型（ET B）基因（Ednr B）的水平未受氯前列醇的影响，但在妊娠中期和晚期（第22天）的子宫中观察到该受体的表达水平显著升高（分别为p = 0.04和0.01），表明ET B在妊娠子宫血管舒张状态中的作用。提示PGF（2 α）引起大鼠子宫胎盘血管收缩，ET-1可能通过激活ETA受体参与了这一作用。子宫胎盘血管收缩诱导缺氧，表现为BOLD MRI的显著变化和VEGF的上调。版权所有（C）2006约翰威利父子有限公司
Blood oxygen level dependent (BOLD) contrast was used to monitor hypoxia induced by cloprostenol, a prostaglandin F-2 alpha (PGF(2 alpha)) analog, in the rat embryo-placental unit (EPU). It is shown that administration of cloprostenol (0.025 mg/rat) at mid-gestation (day 16) reduced EPU oxygenation, as detected by BOLD contrast MRI, in correlation with induction of vascular endothelial growth factor (VEGF) gene (Vegfa) expression in the corresponding placenta (r = 0.56, p = 0.03). Elevated VEGF mRNA expression in response to cloprostenol treatment was also observed at early gestation (day 9) in the forming placenta (p = 0.04) and uterus (p = 0.03). Cloprostenol increased the expression levels of endothelin-1 (ET-1) gene (Edn1) (p = 0.03) and its corresponding peptide (p = 0.02) in the forming placenta, as well as the expression of the endothelin receptor type A (ETA) gene (Ednra) in both the forming placenta (p = 0.009) and the uterus (p = 0.01). The levels of the endothelin receptor type B (ETB) gene (Ednrb) were not affected in response to cloprostenol, but a significant elevation in the expression level of this receptor was observed in the uterus at mid- and late gestation (day 22) (p = 0.04 and 0.01 respectively), suggesting a role for ETB in the vasodilatory status of the pregnant uterus. It is suggested that PGF(2 alpha) induces uteroplacental vasoconstriction in the rat, and that ET-1 may take part in mediating this effect, probably via activation of ETA receptor. The uteroplacental vasoconstriction induces hypoxia, as manifested by significant changes in BOLD MRI and by upregulation of VEGF. Copyright (C) 2006 John Wiley & Sons, Ltd.