Zazerskaya Irina E, Ishkaraeva Valentina V, Frolova Elena V, Solodovnikova Nelly G, Grigorova Yulia N, David Adair C, Fedorova Olga V, Bagrov Alexei Y
Institutes of Neonatology and Heart and Vessels, Almazov Federal Heart, Blood and Endocrinology Center, St. Petersburg, Russia;
Sechenov Institute of Evolutionary Physiology and Biochemistry, St. Petersburg, Russia;
Am J Hypertens. 2013 Nov;26(11):1269-72. doi: 10.1093/ajh/hpt117. Epub 2013 Jul 22.
Immunoneutralization of elevated circulating levels of endogenous digitalis-like Na/K-ATPase inhibitors (i.e. cardiotonic steroids (CTS)) represents a novel approach in the treatment of preeclampsia (PE). Recently we demonstrated that DigiFab (Fab fragments of affinity-purified ovine digoxin antibody) restores PE-induced inhibition of Na/K-ATPase in erythrocytes ex vivo. Previously magnesium ions were shown to antagonize digitalis-induced toxicity, which is mediated by Na/K-ATPase inhibition. We hypothesized that magnesium sulfate would potentiate the effect of DigiFab in the reversal of CTS-induced Na/K-ATPase inhibition.
To test this hypothesis, we studied the ex vivo effect of DigiFab on Na/K-ATPase activity in erythrocytes from patients with PE in the absence and in the presence of 3 mmol/L magnesium sulfate.
Compared with 11 normotensive pregnant subjects (29 ± 1 years; gestational age = 39.0 ± 0.2 weeks; blood pressure = 111 ± 2/73 ± 2 mm Hg), the 12 patients with PE (30 ± 1 years; gestational age = 37.9 ± 0.3 weeks; blood pressure = 159 ± 5/99 ± 3 mm Hg) had plasma levels of marino-bufagenin increased 3-fold (1.38 ± 0.40 vs. 0.38 ± 0.10 nmol/L; P < 0.01) and activity of Na/K-ATPase in erythrocytes was inhibited (1.16 ± 0.11 vs. 2.80 ± 0.20 μmol Pi/ml/h; P < 0.01). Ex vivo, DigiFab (1 µg/ml) restored erythrocyte Na/K-ATPase activity (1.72 ± 0.13 µmol Pi/ml/h; P < 0.01), and 3 mmol magnesium sulfate potentiated the effect of DigiFab (2.30 ± 0.20 µmol Pi/ml/h; P < 0.01).
Magnesium is capable of increasing the efficacy of immunoneutralization of marinobufagenin-induced Na/K-ATPase inhibition.
对内源性洋地黄样钠钾ATP酶抑制剂（即强心甾体（CTS））循环水平升高进行免疫中和是治疗先兆子痫（PE）的一种新方法。最近我们证明，地高辛免疫Fab片段（亲和纯化的羊地高辛抗体的Fab片段）可在体外恢复PE诱导的红细胞钠钾ATP酶抑制。此前有研究表明镁离子可拮抗由钠钾ATP酶抑制介导的洋地黄诱导的毒性。我们推测硫酸镁会增强地高辛免疫Fab片段逆转CTS诱导的钠钾ATP酶抑制的作用。
为验证这一假设，我们研究了在不存在和存在3 mmol/L硫酸镁的情况下，地高辛免疫Fab片段对PE患者红细胞钠钾ATP酶活性的体外作用。
与11名血压正常的孕妇（年龄29±1岁；孕周=39.0±0.2周；血压=111±2/73±2 mmHg）相比，12例PE患者（年龄30±1岁；孕周=37.9±0.3周；血压=159±5/99±3 mmHg）血浆中蟾蜍灵水平升高3倍（1.38±0.40对0.38±0.10 nmol/L；P<0.01），红细胞钠钾ATP酶活性受到抑制（1.16±0.11对2.80±0.20 μmol Pi/ml/h；P<0.01）。在体外，地高辛免疫Fab片段（1 μg/ml）可恢复红细胞钠钾ATP酶活性（1.72±0.13 μmol Pi/ml/h；P<0.01），3 mmol/L硫酸镁可增强地高辛免疫Fab片段的作用（2.30±0.20 μmol Pi/ml/h；P<0.01）。
镁能够提高对蟾蜍灵诱导的钠钾ATP酶抑制进行免疫中和的疗效。
