Gangooly Subrata, Muttukrishna Shanthi, Jauniaux Eric
Institute for Women's Health, University College London, London, United Kingdom.
Institute for Women's Health, University College London, London, United Kingdom; Anu Research Centre, Department of Obstetrics and Gynaecology, University College Cork, Cork University Maternity Hospital, Cork, Republic of Ireland.
PLoS One. 2014 Sep 24;9(9):e107644. doi: 10.1371/journal.pone.0107644. eCollection 2014.
Antihypertensive drugs lower the maternal blood pressure in pre-eclampsia (PE) by direct or central vasodilatory mechanisms but little is known about the direct effects of these drugs on placental functions.
The aim of our study is to evaluate the effect of labetolol, hydralazine, α-methyldopa and pravastatin on the synthesis of placental hormonal and angiogenic proteins know to be altered in PE.
Placental villous explants from late onset PE (n = 3) and normotensive controls (n = 6) were cultured for 3 days at 10 and 20% oxygen (O2) with variable doses anti-hypertensive drugs. The levels of activin A, inhibin A, human Chorionic Gonadotrophin (hCG), soluble fms-like tyrosine kinase-1 (sFlt-1) and soluble endoglin (sEng) were measured in explant culture media on day 1, 2 and 3 using standard immunoassays. Data at day 1 and day 3 were compared.
Spontaneous secretion of sEndoglin and sFlt-1 were higher (p < 0.05) in villous explants from PE pregnancies compared to controls. There was a significant time dependent decrease in the secretion of sFlt-1 and sEndoglin in PE cases, which was seen only for sFlt-1 in controls. In both PE cases and controls the placental protein secretions were not affected by varying doses of anti-hypertensive drugs or the different O2 concentration cultures, except for Activin, A which was significantly (p < 0.05) higher in controls at 10% O2.
Our findings suggest that the changes previously observed in maternal serum hormones and angiogenic proteins level after anti-hypertensive treatment in PE could be due to a systemic effect of the drugs on maternal blood pressure and circulation rather than a direct effect of these drugs on placental biosynthesis and/or secretion.
抗高血压药物通过直接或中枢血管舒张机制降低子痫前期（PE）患者的母体血压，但这些药物对胎盘功能的直接影响知之甚少。
我们研究的目的是评估拉贝洛尔、肼屈嗪、α-甲基多巴和普伐他汀对已知在PE中发生改变的胎盘激素和血管生成蛋白合成的影响。
将晚发型PE患者（n = 3）和血压正常的对照组（n = 6）的胎盘绒毛外植体在10%和20%氧气（O2）条件下，用不同剂量的抗高血压药物培养3天。在第1、2和3天，使用标准免疫测定法测量外植体培养基中激活素A、抑制素A、人绒毛膜促性腺激素（hCG）、可溶性fms样酪氨酸激酶-1（sFlt-1）和可溶性内皮糖蛋白（sEng）的水平。比较第1天和第3天的数据。
与对照组相比，PE妊娠绒毛外植体中sEndoglin和sFlt-1的自发分泌更高（p < 0.05）。PE病例中sFlt-1和sEndoglin的分泌随时间显著减少，而在对照组中仅sFlt-1出现这种情况。在PE病例和对照组中，除激活素A在10% O2时对照组显著更高（p < 0.05）外，不同剂量的抗高血压药物或不同O2浓度培养均未影响胎盘蛋白分泌。
我们的研究结果表明，先前在PE患者抗高血压治疗后母体血清激素和血管生成蛋白水平中观察到的变化，可能是由于药物对母体血压和循环的全身作用，而非这些药物对胎盘生物合成和/或分泌的直接作用。
