Reduced Uterine Perfusion Pressure (RUPP) Model of Preeclampsia in Mice

被引:70
|
作者
Fushima, Tomofumi [1 ,2 ]
Sekimoto, Akiyo [1 ,2 ]
Minato, Takahiro [3 ]
Ito, Takuya [3 ]
Oe, Yuji [4 ]
Kisu, Kiyomi [4 ]
Sato, Emiko [1 ,2 ,4 ]
Funamoto, Kenichi [5 ,6 ]
Hayase, Toshiyuki [6 ]
Kimura, Yoshitaka [3 ]
Ito, Sadayoshi [4 ]
Sato, Hiroshi [1 ,2 ,4 ]
Takahashi, Nobuyuki [1 ,2 ,4 ]
机构
[1] Tohoku Univ, Grad Sch Pharmaceut Sci, Div Clin Pharmacol & Therapeut, Sendai, Miyagi 980, Japan
[2] Fac Pharmaceut Sci, Sendai, Miyagi, Japan
[3] Tohoku Univ, Grad Sch Med, Adv Interdisciplinary Biomed Engn, Sendai, Miyagi, Japan
[4] Tohoku Univ, Grad Sch Med, Div Nephrol Endocrinol & Vasc Med, Sendai, Miyagi, Japan
[5] Tohoku Univ, Japan Frontier Res Inst Interdisciplinary Sci, Sendai, Miyagi 980, Japan
[6] Tohoku Univ, Inst Fluid Sci, 2-1-1 Katahira, Sendai, Miyagi 980, Japan
来源
PLOS ONE | 2016年 / 11卷 / 05期
关键词
ANGIOGENIC FACTORS; HYPERTENSION; PROTEINURIA; ENDOTHELIN; ECLAMPSIA; RATS;
D O I
10.1371/journal.pone.0155426
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
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页数:12
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