1Department of Obstetrics and Gynecology, University of Texas Medical Branch, Galveston, TX, USA.
Reprod Sci. 2014 Jan;21(1):138-45. doi: 10.1177/1933719113492207. Epub 2013 Jun 7.
In order to determine the effects of pravastatin (Pra) on angiogenic and placental hypoxic imbalance in a model of preeclampsia induced by overexpression of soluble fms-like tyrosine kinase 1 (sFlt-1), we randomly allocated pregnant CD1 mice to injection with adenovirus-carrying sFlt-1 or mFc (control). The sFlt-1 group received either Pra (sFlt-1 + Pra) or water (sFlt-1). Mice were sacrificed at day 18, and serum levels of sFlt-1 and soluble endoglin (sEng) were measured. Placental expression of placental (PLGF) and vascular endothelial (VEGF) growth factors and other markers of angiogenesis and hypoxia were assayed. We observed that Pra treatment in sFlt-1 mice reduced sFlt-1 and sEng concentrations at day 18 to levels similar to control group. Placental PLGF and VEGF expression were upregulated, and markers of hypoxia downregulated to levels similar to control group. Hence, Pra prevents the rise in circulating antiangiogenic factors in a mouse model of preeclampsia. Statins may represent a novel approach to prevention of preeclampsia.
为了确定普伐他汀（Pra）对可溶性 fms 样酪氨酸激酶 1（sFlt-1）过表达诱导的子痫前期模型中血管生成和胎盘缺氧失衡的影响，我们将怀孕的 CD1 小鼠随机分配接受携带 sFlt-1 的腺病毒或 mFc（对照）注射。sFlt-1 组接受 Pra（sFlt-1 + Pra）或水（sFlt-1）。在第 18 天处死小鼠，测量血清中 sFlt-1 和可溶性内皮糖蛋白（sEng）的水平。检测胎盘胎盘（PLGF）和血管内皮（VEGF）生长因子等血管生成和缺氧标志物的表达。我们观察到，在 sFlt-1 小鼠中，Pra 治疗可将第 18 天的 sFlt-1 和 sEng 浓度降低至对照组水平。胎盘 PLGF 和 VEGF 的表达上调，而缺氧标志物的表达下调至对照组水平。因此，Pra 可预防子痫前期小鼠模型中循环抗血管生成因子的升高。他汀类药物可能代表预防子痫前期的一种新方法。
