子宫微环境酸碱度改变调控双孔钾离子通道TREK1活性在感染性早产发生中的作用研究

早产发生危害巨大，尚无有效干预手段。感染是诱发早产的重要原因。子宫平滑肌细胞收缩是分娩提前发动的关键事件，但感染触发该事件引起早产的机制尚不明确。我们前期研究发现，妊娠子宫平滑肌细胞膜的钾离子通道TREK1高表达并参与维持子宫静息状态；TREK1失活启动平滑肌细胞收缩；TREK1活性受细胞内外pH变化调控。而TERK1在感染性早产发生中的作用和调控机制不清楚。由此提出科学假设：感染导致子宫微环境pH改变使TREK1失活，启动子宫平滑肌细胞收缩诱发早产。为验证假设，拟利用动物模型和临床病例探讨子宫TREK1基因缺失或变异对早产发生的影响，并从细胞、组织、动物模型和临床病例等层面研究感染后子宫微环境pH变化及其对子宫平滑肌细胞膜上TREK1相关收缩调控功能的影响，以明确TREK1在感染性早产发生中的作用并探讨其调控的分子机制。通过本项目研究，为开发干预感染性早产的新型药物靶点提供理论依据。

Preterm labor is an unpredictable and inevitable fact of life. Infection remains the most important cause of preterm labor. Uterine smooth muscle cell contraction is a key event in labor, but the mechanism by which infection triggers this event to cause preterm labor is still unclear. Previously we found that the potassium channel TREK1 on the membrane of the pregnancy uterus smooth muscle was highly expressed and involved in maintaining the resting state of uterus. TREK1 inactivation initiated smooth muscle cell contraction. TREK1 activity is regulated by intracellular and extracellular pH changes. However, the role and regulatory mechanisms of TERK1 in the occurrence of infection-related preterm labor are unclear. Thus, a scientific hypothesis was put forward: the pH changes of uterine microenvironment caused by infection related TREK1 inactivation, and then the contraction of uterine smooth muscle cells was initiated to induce preterm labor. To verify the hypothesis, we use animal models and clinical cases to explore the uterus TREK1 gene deletion or variation in preterm labor, and we also use cells, tissues, animal models and clinical cohort study after the infection to check the uterine microenvironment pH changes and the uterine smooth muscle cell membrane TREK1 expression and function. Ultimately the TREK1 role in infection-related preterm labor and its molecular mechanisms of regulation will be clarified. The final results will provide important theoretical support for the development of new drug targets for the intervention of infection-related preterm labor.