An imbalance in angiogenic growth factors and poor utero-placental perfusion are strongly associated with preeclampsia. The reduced utero-placental perfusion (RUPP) model that mimics insufficient placental perfusion is used to study preeclampsia. The aim of this study was to develop a refined RUPP model in C57Bl/6 J mice to test the efficacy of MZe786 as a potential inhibitor of soluble Flt-1 for preeclampsia therapy. Murine RUPP (mRUPP) was induced through bilateral ligation of the ovarian arteries at E11.5 that resulted in typical preeclampsia symptoms including increase in mean arterial pressure (MAP), kidney injury and elevated soluble Flt-1 (sFlt-1) levels in the maternal plasma and amniotic fluid. The murine RUPP kidneys showed tubular and glomerular damage along with increased oxidative stress characterised by increased nitrotyrosine staining. The mRUPP displayed abnormal placental vascular histology, reduced expression of placental cystathionine γ-lyase (CSE), the hydrogen sulfide (H₂S) producing enzyme, and resulted in adverse fetal outcomes (FGR). Importantly, oral administration of hydrogen sulfide (H₂S)-releasing compound MZe786 from E11.5 to E17.5 successfully prevented the development of preeclampsia. Specifically, MZe786 treatment reduced maternal MAP and kidney nitrotyrosine staining and improved fetal outcome. The circulation levels of sFlt-1 were dramatically decreased in MZe786 treated animals implying that H₂S released from MZe786 offered protection by inhibiting sFlt-1 levels. MZe786 prevent preeclampsia and warrant a rapid move to randomised control clinical trial.

血管生成生长因子失衡和子宫胎盘灌注不良与先兆子痫密切相关。模拟胎盘灌注不足的减少子宫胎盘灌注 (RUPP) 模型用于研究先兆子痫。本研究的目的是在 C57Bl/6 J 小鼠中开发一个改进的 RUPP 模型，以测试 MZe786 作为可溶性 Flt-1 潜在抑制剂治疗先兆子痫的疗效。小鼠 RUPP (mRUPP) 是通过在 E11.5 处双侧结扎卵巢动脉诱导的，导致典型的先兆子痫症状，包括平均动脉压 (MAP) 升高、肾损伤和可溶性 Flt-1 (sFlt-1) 水平升高。母体血浆和羊水。鼠 RUPP 肾脏显示肾小管和肾小球损伤以及以增加的硝基酪氨酸染色为特征的氧化应激增加。mRUPP 显示胎盘血管组织学异常，胎盘胱硫醚 γ-裂合酶 (CSE)、硫化氢 (H₂ S) 产生酶，并导致不良胎儿结局 (FGR)。重要的是，从 E11.5 到 E17.5 口服释放硫化氢 (H ₂ S) 的化合物 MZe786 成功地预防了先兆子痫的发展。具体而言，MZe786 治疗降低了母体 MAP 和肾脏硝基酪氨酸染色并改善了胎儿结局。在 MZe786 处理的动物中，sFlt-1 的循环水平显着降低，这意味着从 MZe786 释放的 H ₂ S 通过抑制 sFlt-1 水平提供保护。MZe786 可预防先兆子痫，并保证迅速转向随机对照临床试验。