Reduced Uterine Perfusion Pressure (RUPP) Model of Preeclampsia in Mice.
Reduced Uterine Perfusion Pressure (RUPP) Model of Preeclampsia in Mice.
复制标题
小鼠先兆子痫的子宫灌注压力（RUPP）模型降低。
DOI：
10.1371/journal.pone.0155426
复制
发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Takahashi N
中科院分区：
文献类型：
--
作者：
Fushima T;Sekimoto A;Minato T;Ito T;Oe Y;Kisu K;Sato E;Funamoto K;Hayase T;Kimura Y;Ito S;Sato H;Takahashi N
子痫前期(PE)是一种妊娠高血压综合征，伴有蛋白尿，通常在怀孕20周后发生。子宫血流量的减少导致胎盘缺血和胎盘释放抗血管生成因子，如sFlt-1，继而导致PE。尽管子宫灌流压力降低(RUPP)模型在大鼠中得到了广泛的应用，但使用基因工程动物来研究基因在PE中的作用一直是有问题的，因为很难在小鼠身上制造出有用的RUPP模型。为了建立小鼠PE的RUPP模型，我们在出生后14.5天结扎了ICR品系小鼠卵巢分支远端的卵巢血管和/或子宫血管。结果，这些小鼠血压升高，尿白蛋白排泄增加，严重的血管内皮细胞增厚和系膜扩张。她们流产和早产的发生率也增加了。18.5dpc的胚胎重量显著低于假手术组。胚胎离结扎部位越近，吸收率越高，胚胎重量越低。在卵巢血管和子宫血管两者结扎的顺序中，表型更为严重。与文献中描述的Rupp模型不同，该模型不收缩腹主动脉，从而允许使用尾部袖带测量血压。这种新的小鼠RUPP模型对于研究基因工程小鼠PE的发病机制和评估PE的新治疗方法是有用的。
Preeclampsia (PE) is a pregnancy-induced hypertension with proteinuria that typically develops after 20 weeks of gestation. A reduction in uterine blood flow causes placental ischemia and placental release of anti-angiogenic factors such as sFlt-1 followed by PE. Although the reduced uterine perfusion pressure (RUPP) model is widely used in rats, investigating the role of genes on PE using genetically engineered animals has been problematic because it has been difficult to make a useful RUPP model in mice. To establish a RUPP model of PE in mice, we bilaterally ligated ovarian vessels distal to ovarian branches, uterine vessels, or both in ICR-strain mice at 14.5 days post coitum (dpc). Consequently, these mice had elevated BP, increased urinary albumin excretion, severe endotheliosis, and mesangial expansion. They also had an increased incidence of miscarriage and premature delivery. Embryonic weight at 18.5 dpc was significantly lower than that in sham mice. The closer to the ligation site the embryos were, the higher the resorption rate and the lower the embryonic weight. The phenotype was more severe in the order of ligation at the ovarian vessels < uterine vessels < both. Unlike the RUPP models described in the literature, this model did not constrict the abdominal aorta, which allowed BP to be measured with a tail cuff. This novel RUPP model in mice should be useful for investigating the pathogenesis of PE in genetically engineered mice and for evaluating new therapies for PE.