Department of Physiology, Faculty of Medicine, Karadeniz Technical University, Trabzon, Turkey.
Neuroendocrinology. 2022;112(11):1078-1086. doi: 10.1159/000522627. Epub 2022 Feb 16.
BACKGROUND/AIMS: The aim of this study was to determine whether spontaneous and stimulated contractile activity of myometrium in epileptic rats is different from healthy ones, and whether antiepileptic drugs (AEDs) have any direct influence on myometrial contractility.
Myometrial strips from nonpregnant and pregnant adult epileptic WAG/Rij and Wistar rats were suspended in organ bath containing physiological salt solution (37°C and pH 7.4, aerated with 95% oxygen-5% CO2), and isometric contractions were recorded. Effects of cumulative concentrations of selected AEDs including phenytoin, levetiracetam, and valproic acid alone and in combination on oxytocin-induced contractions was examined. Contractile parameters assessed included the area under curve, amplitude, and frequency of contractions, evaluated by 10-min periods. Data were analyzed using one-way analysis of variance and Tukey HSD test.
Spontaneous myometrial contractility and responses to oxytocin showed species difference. Compared with that of control Wistar rats, spontaneous contractions of myometrium from nonpregnant epileptic WAG/Rij rats were significantly higher while being significantly lower in pregnant preparations. Upon stimulation with oxytocin, WAG/Rij myometrium showed significantly lower contractile response compared with preparations from healthy control Wistars (p < 0.01). Phenytoin and valproate caused concentration-dependent significant attenuation (p < 0.05) of spontaneous and oxytocin-induced contractions of myometrium from WAG/Rij and Wistar rats, both nonpregnant and pregnant.
Myometrial smooth muscle from epileptic rats showed different spontaneous and oxytocin-induced contractility, and AEDs showed contractile modulatory actions, phenytoin being the most and levetiracetam the least effective. Although in vitro, our findings may be of clinical implications with regard to obstetric complications in epileptics and use of AEDs during pregnancy, and warrants further investigations.
背景/目的：本研究旨在确定癫痫大鼠的子宫自发性和刺激性收缩活动是否与健康大鼠不同，以及抗癫痫药物（AEDs）是否对子宫收缩有直接影响。
将来自非妊娠和妊娠成年癫痫 Wag/Rij 和 Wistar 大鼠的子宫带条悬挂在含有生理盐水的器官浴中（37°C，pH7.4，用 95%氧气-5%CO2 充气），并记录等长收缩。检查了选定的 AED 包括苯妥英、左乙拉西坦和丙戊酸单独和联合对催产素诱导收缩的累积浓度的影响。通过 10 分钟时间段评估收缩参数，包括收缩的曲线下面积、幅度和频率。使用单向方差分析和 Tukey HSD 检验分析数据。
子宫自发性收缩性和对催产素的反应表现出种间差异。与对照 Wistar 大鼠相比，非妊娠癫痫 Wag/Rij 大鼠的子宫自发性收缩明显增加，而妊娠制剂则明显降低。在催产素刺激下，Wag/Rij 子宫的收缩反应明显低于健康对照 Wistar 制剂（p < 0.01）。苯妥英和丙戊酸导致来自 Wag/Rij 和 Wistar 大鼠的子宫自发性和催产素诱导收缩的浓度依赖性显著减弱（p < 0.05），无论是否妊娠。
癫痫大鼠的子宫平滑肌表现出不同的自发性和催产素诱导收缩性，AEDs 表现出收缩调节作用，苯妥英作用最强，左乙拉西坦作用最弱。尽管是在体外，但我们的发现可能对癫痫患者的产科并发症和怀孕期间使用 AEDs 具有临床意义，并需要进一步研究。
