Discovery of a spontaneous genetic mouse model of preeclampsia
Discovery of a spontaneous genetic mouse model of preeclampsia
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DOI：
10.1161/hy02t2.102904
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发表时间：
2002-02-01
期刊：
影响因子：
8.3
通讯作者：
Bates, JN
中科院分区：
文献类型：
--
作者：
Davisson, RL;Hoffmann, DS;Bates, JN
先兆子痫仍然是母亲和胎儿发病率和死亡率的主要原因，但病因不明。基线血压升高的女性患这种疾病的风险增加。我们假设BPH/5小鼠（一种具有轻度血压升高的近交系小鼠品系）会发生妊娠高血压综合征。非妊娠雌性BPH/5和C57 BL/6小鼠胸主动脉植入遥测仪。在7天的恢复期和5天的基线平均动脉血压（MAP）记录后，进行品系匹配的定时交配。在妊娠期间和出生后1周连续记录MAP。在代谢笼中的单独小鼠中，跟踪尿蛋白，然后进行肾组织学分析。在妊娠前，BPH/5品系的基线MAP高于C57 BL/6品系，但两种品系的总尿蛋白水平和肾组织学相似。在妊娠的前2周，两组的MAP保持稳定。然而，在最后三个月开始时，BPH/5小鼠的MAP开始进一步上升;它在分娩前上升到峰值水平，并在分娩后2天恢复到孕前水平。这是伴随着妊娠晚期蛋白尿和进行性肾小球硬化。在C57 BL/6组中未观察到任何变化，但在妊娠中期MAP略有下降。BPH/5组分娩的窝仔数明显较小，尽管妊娠早期胎儿数量正常，纵向超声研究记录了高血压和肾脏疾病发作前的胎儿死亡。这是第一个报告的动物模型，自发发展的综合征，承担密切相似的先兆子痫，它应该有一个影响，我们了解这种疾病的病理生理。
Preeclampsia remains a leading cause of maternal and fetal morbidity and mortality but has an unknown etiology. Women with elevated baseline blood pressure have an increased risk of this disorder. We hypothesized that BPH/5 mice, an inbred mouse strain with mildly elevated blood pressure, would develop a pregnancy-induced hypertensive syndrome. Nonpregnant female BPH/5 and C57BL/6 mice underwent thoracic aortic implantation of telemeters. After 7 days of recovery and 5 days of baseline mean arterial blood pressure (MAP) recording, strain-matched timed matings were carried out. MAP was recorded continuously during pregnancy and for I week after birth. In separate mice in metabolic cages, urinary protein was tracked, followed by renal histological analysis. Before pregnancy, the BPH/5 strain had elevated baseline MAP compared with the C57BL/6 strain, but both strains had similar total urinary protein levels and renal histology. MAP remained stable in both groups during the first 2 weeks of pregnancy. However, at the start of the last trimester, MAP began to rise further in the BPH/5 mice; it rose to peak levels just before deliver and returned to prepregnancy levels by 2 days after delivery. This was accompanied by late-gestational proteinuria and progressive glomerulosclerosis. No changes were observed in the C57BL/6 group except for a small decrease in MAP at mid gestation. The BPH/5 group delivered significantly smaller litters despite normal numbers of fetuses early in gestation, and longitudinal ultrasound studies documented fetal demise before the onset of hypertension and renal disease. This is the first report of an animal model that spontaneously develops a syndrome that bears close resemblance to preeclampsia, and it should have an impact on our understanding of the pathophysiology of this disorder.