Department of Molecular and Cellular Physiology, University Department, Harris-Wellbeing Preterm Birth Research Centre, Institute of Translational Medicine, University of Liverpool, First floor Liverpool Women's Hospital, Crown Street, Liverpool, L8 7SS, UK.
Reprod Sci. 2020 Aug;27(8):1570-1579. doi: 10.1007/s43032-020-00185-8.
Magnesium sulfate is used as a tocolytic, but clinical efficacy has been seriously questioned. Our objective was to use controlled ex vivo conditions and known pregnancy stages, to investigate how 2 key factors, hormones and gestation, affect magnesium's tocolytic ability. We hypothesized that these factors could underlie the varying clinical findings around magnesium's efficacy. Myometrial strips were obtained from nonpregnant (n = 10), mid-pregnant (n = 12), and term-pregnant (n = 11) mouse uterus. The strips were mounted in organ baths superfused with oxygenated physiological saline at pH 7.4 and 37 °C. The effect of different concentrations of MgSO (2-20 mM) was examined on spontaneous and oxytocin-induced (0.5-1 nM) contractions. Contractile properties (amplitude, frequency, and area under the curve) were measured before and after application of magnesium. Magnesium sulfate had a dose-dependent inhibitory effect on both spontaneous and oxytocin-induced contractions but was less effective in the presence of oxytocin. In spontaneous contractions, magnesium was more potent as gestation progressed (P < .0001). In the presence of oxytocin, however, there were no significant gestational differences in its effects on contraction. The rapid onset and reversal of magnesium's effects suggest an extracellular action on calcium entry. Taken together, we conclude that magnesium's actions are influenced by both gestational state and hormones, such that, at least in mice, it is least effective in early gestation with oxytocin present and most effective at term in the absence of oxytocin. That magnesium is least effective preterm and oxytocin decreases its effectiveness throughout gestation, may explain its disappointing clinical effects as a tocolytic.
硫酸镁被用作一种保胎药，但临床疗效一直受到严重质疑。我们的目的是利用体外控制条件和已知的妊娠阶段，研究 2 个关键因素（激素和妊娠）如何影响镁的保胎作用。我们假设这些因素可能是导致镁保胎疗效差异的原因。我们从非妊娠（n = 10）、妊娠中期（n = 12）和足月妊娠（n = 11）的小鼠子宫中获得了子宫肌条。将这些肌条安装在器官浴中，用充氧生理盐水在 pH 值为 7.4 和 37°C 的条件下进行超灌注。研究了不同浓度的硫酸镁（2-20 mM）对自发性和催产素诱导（0.5-1 nM）收缩的影响。在应用镁前后测量收缩的特性（幅度、频率和曲线下面积）。硫酸镁对自发性和催产素诱导的收缩均有剂量依赖性抑制作用，但在存在催产素的情况下效果较差。在自发性收缩中，随着妊娠的进展，镁的作用变得更强（P <.0001）。然而，在存在催产素的情况下，其对收缩的作用在妊娠期间没有明显的差异。镁作用的快速起始和逆转表明其对钙内流具有细胞外作用。综上所述，我们得出结论，镁的作用受到妊娠状态和激素的影响，至少在小鼠中，它在存在催产素的早期妊娠中效果最差，在没有催产素的足月妊娠中效果最佳。镁在早产时效果最差，催产素降低其在整个妊娠期间的效果，这可能解释了它作为保胎药令人失望的临床效果。
