Gabor Than Award Lecture 2008: Pre-eclampsia - From Placental Oxidative Stress to Maternal Endothelial Dysfunction
Gabor Than Award Lecture 2008: Pre-eclampsia - From Placental Oxidative Stress to Maternal Endothelial Dysfunction
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DOI：
10.1016/j.placenta.2008.11.020
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发表时间：
2009-03-01
期刊：
影响因子：
3.8
通讯作者：
Cindrova-Davies, T.
中科院分区：
文献类型：
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作者：
Cindrova-Davies, T.
先兆子痫是世界范围内人类妊娠最重要的并发症，也是孕产妇和胎儿发病率和死亡率的主要原因。强有力的证据表明，胎盘氧化应激的产生，继发于螺旋动脉重塑不足，是一个关键的中间事件，触发胎盘因子的混合物的分泌，最终导致母体炎症反应的增强。活性氧（ROS）已被确认为细胞内信号级联的第二信使。在分娩过程中体外或体内研究胎盘缺血-再灌注的实验提供了强有力的证据，表明氧化应激和ROS产生可以激活下游应激信号传导途径p38和SAPK/JNK MAPK以及促炎性NF-κ B信号传导途径，最终释放炎性介质、凋亡碎片、抗血管生成因子和其他介质，然后刺激母体炎症反应，表现为内皮功能障碍和先兆子痫的症状。在体外添加抗氧化剂或阻断应激或炎症途径可减弱这些作用，并为治疗干预提供可能性。(C)2009年由IFPA和Elsevier Ltd.出版
Pre-eclampsia is the most important complication of human pregnancy worldwide and a major contributor to maternal and fetal morbidity and mortality. Strong evidence exists that generation of placental oxidative stress, secondary to deficient spiral artery remodelling, is a key intermediary event, triggering the secretion of a mixture of placental factors that culminate in an enhanced maternal inflammatory response. Reactive oxygen species (ROS) have been recognised as secondary messengers in intracellular signalling cascades. Experiments studying placental ischaemia-reperfusion in vitro or in vivo during labour provide strong evidence suggesting that oxidative stress and ROS production can activate downstream stress-signalling pathways, p38 and SAPK/JNK MAPK, and the pro-inflammatory NF-kappa B signalling pathway, culminating in the release of inflammatory mediators, apoptotic debris, anti-angiogenic factors and other mediators, which then stimulate a maternal inflammatory reaction that manifests in endothelial dysfunction and the symptoms of pre-eclampsia. Addition of anti-oxidants or blocking the stress or inflammatory pathways in vitro attenuates these effects and opens possibilities for therapeutic intervention. (C) 2009 Published by IFPA and Elsevier Ltd.