牛磺酸抑制妊娠期子宫平滑肌收缩的分子机制研究

The functional disorder of myometrium contraction will inevitably increase the risk of premature birth during the process of pregnancy, which will affect the health and even lead to death for puerperant and neonate. These problems have become urgent for obstetrician. Taurine has many kinds of biological functions such as the regulatioon of ion channels and the relaxation of arterial smooth muscle.It was demonstrated that the concentration of taurine gradually reduce and the expression of taurine transport in myometrium during the process of pregnancy. Before and after adding of taurine and its antagonist,The project on the basis of previous works intends to observe the effect of the taurine on the myometrium using in-vitro uterus model during pregnancy by means of isometric tension recordings.Taurine and the inhibitor of BKCa channel were add to fresh isolated uterine smooth muscle cell to study the expressions of transcriptional gene of BKCa channel subtypes by using RT-PCR.The physiological effect of taurine in the level of tissue,cell and moledcular was evaluated to testify the hypothesis that taurine inhibits the contraction of myometrium by means of its molecular target, BKCa channel. The project will explore the mechanism for maintaining quiescent condition and starting labor and provide the new ideas of prevention and treatment of premature delivery.

妊娠期子宫平滑肌收缩功能紊乱势必增加早产的风险，危及母婴健康甚至生命，已成为产科医生亟待解决的问题。牛磺酸具有调节离子通道、松弛动脉平滑肌等多种生物学功能。我们前期证实妊娠期子宫平滑肌牛磺酸含量逐渐降低和牛磺酸转运体蛋白、基因的表达。本项目在前期工作的基础上，拟结合妊娠小鼠子宫自发收缩模型，给予牛磺酸及其拮抗剂前后，采用等长张力实验观察牛磺酸对子宫平滑肌收缩作用的影响。以妊娠子宫平滑肌细胞为研究对象，给予牛磺酸和BKCa通道阻断剂前后，运用RT-PCR检测BKCa通道亚基在转录水平的表达，观察牛磺酸对BKCa通道的调控作用。通过评估牛磺酸在组织、细胞和分子三个水平产生的生理效应，验证牛磺酸抑制妊娠子宫平滑肌收缩的分子靶点是BKCa通道的假说，探寻妊娠期子宫平滑肌静息状态维持和分娩启动的分子机制，为早产的预防和治疗提供新的思路。

本项目成功建立妊娠小鼠子宫自发收缩模型，运用HPLC检测了妊娠期小鼠子宫平滑肌牛磺酸含量；给予牛磺酸及其拮抗剂前后，采用等长张力实验观察牛磺酸对子宫平滑肌收缩作用的影响。以妊娠子宫平滑肌细胞为研究对象，给予不同浓度的牛磺酸后，运用RT-PCR检测BKCa通道亚基在转录水平，观察牛磺酸对BKCa通道的调控作用。结果显示妊娠期小鼠子宫平滑肌牛磺酸含量在临近分娩时降低，分娩后回升，表明Tau可能参与调控分娩的启动。牛磺酸对妊娠子宫平滑肌的收缩活动有抑制作用，这一分子机制依赖于对BKCa通道的调控α亚基的调控。通过评估牛磺酸在组织、细胞和分子三个水平产生的生理效应，证实了牛磺酸抑制妊娠子宫平滑肌收缩的分子靶点是BKCa通道的假说，阐明了妊娠期子宫平滑肌静息状态维持和分娩启动的分子机制，表明牛磺酸有望成为治疗早产的安胎药，为早产的预防和治疗提供了新的策略。