Department of Obstetrics and Gynecology, Anhui Medical University, Hefei, China; Anhui Province Key Laboratory of Reproductive Health and Genetics, Anhui Medical University, Hefei, China; Anhui Provincial Engineering Technology Research Center for Biopreservation and Artificial Organs, The First Affiliated Hospital, Anhui Medical University, Hefei, China.
Department of Obstetrics and Gynecology, Anhui Medical University, Hefei, China.
Biochem Pharmacol. 2018 Jun;152:252-263. doi: 10.1016/j.bcp.2018.03.021. Epub 2018 Mar 22.
Quiescence of myometrium contractile activity allows uterine expansion to accommodate the growing fetus and prevents preterm labor particularly during excessive uterine stretch in multiple pregnancy. However, the mechanisms regulating uterine response to stretch are unclear. We tested the hypothesis that prolonged uterine stretch is associated with decreased myometrium contractile activity via activation of TWIK-related K channel (TREK-1). Pregnant women at different gestational age (preterm and term) and uterine stretch (singleton and twin pregnancy) were studied, and uterine strips were isolated for measurement of contractile activity and TREK-1 channel expression/activity. Both oxytocin- and KCl-induced contraction were reduced in term vs preterm pregnancy and in twin vs singleton pregnancy. Oxytocin contraction was reduced in uterine segments exposed to 8 g stretch compared to control tissues under 2 g basal tension. TREK-1 mRNA expression and protein levels were augmented in Singleton-Term vs Singleton-Preterm, and in uterine strips exposed to 8 g stretch. The TREK-1 activator arachidonic acid reduced oxytocin contraction in preterm and term, singleton and twin pregnant uterus. The TREK-1 blocker l-methionine enhanced oxytocin contraction in Singleton-Term and twin pregnant uterus, and reversed the decreases in contraction in uterine strips exposed to prolonged stretch. Carboprost-induced uterine contraction was also reduced by arachidonic acid and enhanced by l-methionine. Thus, myometrium contraction decreases with gestational age and uterine expansion in twin pregnancy. The results suggest that prolonged stretch enhances the expression/activity of TREK-1 channel, leading to decreased myometrium contractile activity and maintained healthy term pregnancy particularly in multiple pregnancy.
子宫平滑肌收缩活动的静止状态允许子宫扩张以适应不断成长的胎儿，防止早产，尤其是在多胎妊娠中子宫过度拉伸时。然而，调节子宫对拉伸反应的机制尚不清楚。我们假设，通过 TWIK 相关钾通道（TREK-1）的激活，长时间的子宫拉伸与子宫平滑肌收缩活动减少有关。研究了不同妊娠周数（早产和足月）和子宫拉伸（单胎和双胎妊娠）的孕妇，并分离子宫条进行收缩活动和 TREK-1 通道表达/活性的测量。与早产相比，足月妊娠和与单胎妊娠相比，双胎妊娠中催产素和氯化钾诱导的收缩均减少。与 2g 基础张力下的对照组织相比，暴露于 8g 拉伸下的子宫段中催产素收缩减少。TREK-1mRNA 表达和蛋白水平在 Singleton-Term 与 Singleton-Preterm 之间以及在暴露于 8g 拉伸的子宫条中增加。TREK-1 激活剂花生四烯酸降低了早产和足月、单胎和双胎妊娠子宫的催产素收缩。TREK-1 阻断剂 L-蛋氨酸增强了 Singleton-Term 和双胎妊娠子宫中催产素的收缩，并逆转了暴露于长时间拉伸的子宫条中收缩减少的情况。花生四烯酸也降低了卡前列素诱导的子宫收缩，L-蛋氨酸增强了这种收缩。因此，随着妊娠年龄的增加和双胎妊娠中子宫的扩张，子宫平滑肌收缩减少。结果表明，长时间的拉伸增强了 TREK-1 通道的表达/活性，导致子宫平滑肌收缩活动减少，并维持了健康的足月妊娠，特别是在多胎妊娠中。
