Myatt L, Kossenjans W, Sahay R, Eis A, Brockman D
Department of Obstetrics and Gynecology, University of Cincinnati College of Medicine, Ohio 45267-0526, USA.
J Matern Fetal Med. 2000 Jan-Feb;9(1):79-82. doi: 10.1002/(SICI)1520-6661(200001/02)9:1<79::AID-MFM16>3.0.CO;2-O.
Increased production of superoxide and nitric oxide may produce oxidative stress in the placenta by formation of the prooxidant peroxynitrite, which itself causes vascular dysfunction. Nitrotyrosine residues, which are a marker of peroxynitrite formation and action, are found in placental vessels of preeclamptic and diabetic pregnancies, indicating oxidative stress. Treatment of the placental vasculature with authentic peroxynitrite in vitro attenuates responses both to vasoconstrictors such as the thromboxane mimetic U46619 and to vasodilators, including glyceryl trinitrate and prostacyclin, indicating it has caused vascular dysfunction. Further, the responses of the fetal-placental vasculature of diabetic and preeclamptic placentae to these same vasoconstrictor and vasodilator agents are significantly attenuated when compared to responses in normal control placentae. Together these data suggest there may be a cause and effect relationship between formation and action of peroxynitrite and vascular dysfunction in the placenta of both preeclamptic and diabetic pregnancies. The presence of such attenuated vascular responses indicates that perhaps the placenta may not be able to adequately respond to demands for altered blood flow in situations where this is necessary in preeclamptic or diabetic pregnancies, thus leading to further fetal compromise.
超氧化物和一氧化氮生成增加可能通过促氧化剂过氧亚硝酸盐的形成在胎盘中产生氧化应激，而过氧亚硝酸盐本身会导致血管功能障碍。硝基酪氨酸残基是过氧亚硝酸盐形成和作用的标志物，在子痫前期和糖尿病妊娠的胎盘血管中被发现，表明存在氧化应激。在体外用过氧亚硝酸盐处理胎盘血管系统会减弱对血管收缩剂（如血栓素类似物U46619）和血管扩张剂（包括硝酸甘油和前列环素）的反应，表明它已导致血管功能障碍。此外，与正常对照胎盘相比，糖尿病和子痫前期胎盘的胎儿-胎盘血管系统对这些相同的血管收缩剂和血管扩张剂的反应明显减弱。这些数据共同表明，在子痫前期和糖尿病妊娠的胎盘中，过氧亚硝酸盐的形成和作用与血管功能障碍之间可能存在因果关系。这种减弱的血管反应表明，在子痫前期或糖尿病妊娠中需要改变血流的情况下，胎盘可能无法充分响应血流变化的需求，从而导致进一步的胎儿受损。
