Redman C W G, Sargent I L
Nuffield Department of Obstetrics and Gynaecology, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, UK.
Placenta. 2009 Mar;30 Suppl A:S38-42. doi: 10.1016/j.placenta.2008.11.021. Epub 2009 Jan 12.
In pre-eclampsia, poor placentation causes both oxidative and endoplasmic reticulum stress of the placenta. It is believed placental hypoxia stimulates excessive production of soluble fms-like tyrosine kinase 1 (sFlt-1), which binds and deactivates circulating vascular endothelial growth factor (VEGF). When maternal endothelium is deprived of VEGF it becomes dysfunctional hence leading to the clinical syndrome of the mother. In this paper the previous claim that poor placentation may predispose more to placental oxidative stress than hypoxia is reiterated. We show why pre-eclampsia is not only an endothelial disease, but also a disorder of systemic inflammation. We question that hypoxia is the only or indeed the main stimulus to release of sFlt-1; and emphasise the role of inflammatory mechanisms. Hypoxia cannot be assumed simply because hypoxia-inducible transcription factors (HIF) are upregulated. Concurrent assessments of nuclear factor-kappaB (NF-kappaB), a transcription factor for inflammatory responses are desirable to obtain a more complete picture. We point out that the pre-eclampsia placenta is the source of bioactive circulating factors other than sFlt-1 in concentrations that are much higher than in normal pregnancy. These may also contribute to the final inflammatory syndrome. We propose a modified version of the two-stage model for pre-eclampsia.
在子痫前期，胎盘着床不佳会导致胎盘的氧化应激和内质网应激。据信，胎盘缺氧会刺激可溶性fms样酪氨酸激酶1（sFlt-1）过度产生，sFlt-1会结合并使循环中的血管内皮生长因子（VEGF）失活。当母体内皮细胞缺乏VEGF时，就会功能失调，从而导致母亲出现临床综合征。在本文中，我们重申了之前的观点，即胎盘着床不佳可能比缺氧更容易引发胎盘氧化应激。我们展示了子痫前期为何不仅是一种内皮疾病，也是一种全身炎症性疾病。我们质疑缺氧是否是释放sFlt-1的唯一或主要刺激因素，并强调炎症机制的作用。不能仅仅因为缺氧诱导转录因子（HIF）上调就认定存在缺氧。同时评估核因子-κB（NF-κB）（一种炎症反应的转录因子）有助于更全面地了解情况。我们指出，子痫前期胎盘是除sFlt-1之外生物活性循环因子的来源，其浓度远高于正常妊娠时的浓度。这些因子也可能导致最终的炎症综合征。我们提出了一个子痫前期两阶段模型的修改版本。
