Ohta Hidenobu, Kaga Maiko, Li Heng, Sakai Hiromi, Okamura Kunihiro, Yaegashi Nobuo
Department of Psychophysiology, National Institute of Mental Health, National Center of Neurology and Psychiatry, Kodaira, Tokyo 187-8553, Japan.
Department of Psychiatry, Asai Hospital, Togane, Chiba 283-0042, Japan.
J Funct Biomater. 2017 Jul 30;8(3):32. doi: 10.3390/jfb8030032.
The molecular mechanisms of pre-eclampsia are being increasingly clarified in animals and humans. With the uncovering of these mechanisms, preventive therapy strategies using chronic infusion of adrenomedullin, vascular endothelial growth factor-121 (VEGF-121), losartan, and sildenafil have been proposed to block narrow spiral artery formation in the placenta by suppressing related possible factors for pre-eclampsia. However, although such preventive treatments have been partly successful, they have failed in ameliorating fetal growth restriction and carry the risk of possible side-effects of drugs on pregnant mothers. In this study, we attempted to develop a new symptomatic treatment for pre-eclampsia by directly rescuing placental ischemia with artificial oxygen carriers (hemoglobin vesicles: HbV) since previous data indicate that placental ischemia/hypoxia may alone be sufficient to lead to pre-eclampsia through up-regulation of sFlt-1, one of the main candidate molecules for the cause of pre-eclampsia. Using a rat model, the present study demonstrated that a simple treatment using hemoglobin vesicles for placental ischemia rescues placental and fetal hypoxia, leading to appropriate fetal growth. The present study is the first to demonstrate hemoglobin vesicles successfully decreasing maternal plasma levels of sFlt-1 and ameliorating fetal growth restriction in the pre-eclampsia rat model (p < 0.05, one-way ANOVA). In future, chronic infusion of hemoglobin vesicles could be a potential effective and noninvasive therapy for delaying or even alleviating the need for Caesarean sections in pre-eclampsia.
子痫前期的分子机制在动物和人类中越来越清晰。随着这些机制的揭示，有人提出通过长期输注肾上腺髓质素、血管内皮生长因子-121（VEGF-121）、氯沙坦和西地那非进行预防性治疗，以通过抑制子痫前期的相关可能因素来阻止胎盘螺旋动脉狭窄的形成。然而，尽管这种预防性治疗取得了部分成功，但它们未能改善胎儿生长受限，并且存在药物对孕妇可能产生副作用的风险。在本研究中，我们试图开发一种新的子痫前期对症治疗方法，即通过人工氧载体（血红蛋白囊泡：HbV）直接挽救胎盘缺血，因为先前的数据表明，胎盘缺血/缺氧可能单独就足以通过上调子痫前期主要候选分子之一的sFlt-1来导致子痫前期。本研究使用大鼠模型表明，使用血红蛋白囊泡治疗胎盘缺血可挽救胎盘和胎儿缺氧，从而实现胎儿的正常生长。本研究首次证明血红蛋白囊泡成功降低了子痫前期大鼠模型中母体血浆sFlt-1水平并改善了胎儿生长受限（p<0.05，单因素方差分析）。未来，长期输注血红蛋白囊泡可能成为一种潜在的有效且无创的治疗方法，用于延迟甚至减少子痫前期剖宫产的需求。
