The Nephrology/Hypertension Division, Department of Medicine, Texas A&M Health Science Center/Scott & White, Temple, Texas 76508, USA.
Am J Perinatol. 2010 Apr;27(4):299-305. doi: 10.1055/s-0029-1241739. Epub 2009 Oct 12.
Preeclampsia (PE) is a disorder that results in significant fetomaternal morbidity and mortality with yet no definitive pharmacological intervention. It involves the development of de novo hypertension and proteinuria after 20 weeks of pregnancy. All too often, intrauterine growth restriction (IUGR) occurs. Evidence has accrued that implicates the cardiac glycosides (the cardenolides and the bufadienolides) as potentially involved in the pathophysiology of PE. These compounds act by inhibiting Na(+)/K(+) ATPase. Digibind (digoxin immune Fab) antagonizes this action of the cardenolides. It also has cross-reactivity against the bufadienolides, including marinobufagenin. This study investigated the effects of Digibind in a rat model of PE. We induced a syndrome in rats, which includes many of the phenotypic characteristics of human PE. Digibind, in escalating doses, was given on days 10 to 20 of pregnancy. Digibind produced significant lowering of the blood pressure and reduced proteinuria in our rat model of PE. However, it also did not avert IUGR. In view of these findings, in our experimental model of human PE, further studies in the quest for effective treatment of PE need to focus on pharmaceuticals that can remedy the syndrome without compromising the fetus.
子痫前期 (PE) 是一种导致严重母婴发病率和死亡率的疾病，但目前尚无明确的药物干预措施。它涉及到妊娠 20 周后新出现的高血压和蛋白尿。常常伴有胎儿宫内生长受限 (IUGR)。有证据表明，强心苷（卡烯内酯和蟾蜍内酯）可能与 PE 的病理生理学有关。这些化合物通过抑制 Na(+)/K(+)ATP 酶起作用。地高辛免疫 Fab（Digibind）拮抗卡烯内酯的这种作用。它还对蟾蜍内酯具有交叉反应性，包括蟾蜍灵。本研究在 PE 的大鼠模型中研究了 Digibind 的作用。我们在大鼠中诱导了一种综合征，其中包括许多人类 PE 的表型特征。在妊娠第 10 天至第 20 天给予递增剂量的 Digibind。Digibind 显著降低了我们的 PE 大鼠模型的血压并减少了蛋白尿。然而，它也没有避免 IUGR。鉴于这些发现，在我们的人类 PE 实验模型中，为了寻找有效的 PE 治疗方法，进一步的研究需要集中在可以治疗该综合征而不损害胎儿的药物上。
