Reduced uterine perfusion pressure induces hypertension in the pregnant mouse
Reduced uterine perfusion pressure induces hypertension in the pregnant mouse
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DOI：
10.1152/ajpregu.00268.2014
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发表时间：
2014-12-01
影响因子：
2.8
通讯作者：
Alexander, Barbara T.
中科院分区：
文献类型：
--
作者：
Intapad, Suttira;Warrington, Junie P.;Alexander, Barbara T.
尽管子痫前期是孕产妇死亡的主要原因之一，也是孕产妇和围产儿发病率的主要贡献者，但其发病机制尚未完全阐明。越来越多的证据表明，子宫胎盘灌注减少和由此导致的胎盘缺血触发了导致这种母体疾病的一连串事件。虽然已建立的子宫灌流压力降低(RUPP)的大鼠模型为先兆子痫的病因提供了宝贵的见解，但本研究的目的是建立一种子宫灌流降低的小鼠模型，以通过与新的基因靶向小鼠结合来扩展机制研究。为了达到这一目的，C57BL/6J小鼠在妊娠第13天开始进行假手术或限制腹主动脉和卵巢动脉的血流。在妊娠第18天，在清醒的、长期使用仪器的小鼠中测得的平均动脉压在RUPP组(120+/-4毫米汞柱)显著高于假手术组(104+/-4毫米汞)(P<；0.01)。胎盘缺血在妊娠第18天降低胎儿体重(0.95+/-0.04和0.80+/-0.02g；RUPP与Sham相比；P+/-0.02)，并增加循环中抗血管生成的FMS相关酪氨酸激酶(SFlt)-1(P<；0.05)水平。先兆子痫患者的血浆sFlt-1浓度升高，并对大鼠子宫灌注量减少作出反应。因此，这些结果表明，子宫灌注量减少的小鼠模型适用于从新的机制上研究妊娠期间胎盘缺血引起的高血压的病因。
Despite preeclampsia being one of the leading causes of maternal death and a major contributor of maternal and perinatal morbidity, the mechanisms responsible for its pathogenesis have yet to be fully elucidated. Growing evidence indicates that reduced uteroplacental perfusion and the resulting placental ischemia triggers the cascade of events leading to this maternal disorder. While the well-established rat model of reduced uterine perfusion pressure (RUPP) is providing invaluable insight into the etiology of preeclampsia, the aim of this study was to develop a mouse model of reduced uterine perfusion to expand mechanistic investigation by incorporation with novel genetargeted mice. To accomplish this aim, a sham surgical procedure or a restriction of blood flow at the abdominal aorta and the ovarian arteries was initiated at day 13 of gestation in C57BL/6J mice. Mean arterial pressure measured in conscious, chronically instrumented mice was significantly elevated in the RUPP (120 +/- 4 mmHg) compared with the sham (104 +/- 4 mmHg) mice at day 18 of gestation (P < 0.01). Placental ischemia reduced fetal weights (0.95 +/- 0.04 and 0.80 +/- 0.02 g; RUPP vs. Sham, respectively; P +/- 0.02) and increased circulating levels of antiangiogenic soluble fms-related tyrosine kinases (sFlt)-1 (P < 0.05) in the RUPP at day 18 of gestation. Plasma concentrations of sFlt-1 are increased in preeclamptic patients and in response to reduced uterine perfusion in the rat. Thus, these results suggest that the mouse model of reduced uterine perfusion is applicable to facilitate novel mechanistic investigation into the etiology of hypertension that results from placental ischemia during pregnancy.