CTRP家族在孕期睡眠质量下降致糖脂代谢紊乱中的作用研究

Poor sleep quality is prevalent during pregnancy and is associated with a series of adverse outcomes. Studies have shown that the adipokines family CTRP is associated with sleep quality, and several family members play an important role in glycolipid metabolism. We reported for the first time that CTRP3 is present in cord blood and might be involved in fetal growth, we also found that pregnant women with poor sleep quality had an increased risk of gestational diabetes. However, it is not clear that whether sleep quality could changes the secretion levels of CTRP family members in the maternal blood, and then leading to the disorders of glycolipid metabolism. Therefore, this project intends to analyze the role of sleep quality on CTRP family members (adiponectin, CTRP1, 3, 5, 9 and 13) and the role of CTRP family members on glycolipid metabolism in pregnant women by questionnaire, actiwatch and biochemical data in a prospective cohort. Futhermore, we would establish an sleep deprivation model in pregnant mice to validate the resluts of human research. This project will be based on the CTRP family for the first time to explore the role of sleep on glycolipid metabolism in pregnant women, and propose possible biological mechanisms on the health effects of pregnant women and offspring from the perspective of biological rhythm.

睡眠质量下降在孕期普遍存在并与一系列不良妊娠结局有关。研究显示脂肪因子家族CTRP与睡眠质量相关，且多个家族成员在糖脂代谢中发挥重要作用。申报人首次报道在脐血中发现CTRP3，并提示与胎儿生长发育相关；前期研究发现，睡眠质量差的孕妇妊娠期糖尿病发生风险增加。睡眠是否通过改变母体内CTRP家族成员分泌水平，进而导致糖脂代谢紊乱尚不明确。因此，本项目拟通过前瞻性队列研究，利用问卷、腕表和生化检查数据，分析睡眠质量对孕妇血CTRP家族成员（脂联素，CTRP1，3，5，9和13）的影响，进一步探讨CTRP在孕期糖脂代谢紊乱中的作用。通过建立孕鼠睡眠剥夺模型，验证人群研究的结果。本项目将首次基于CTRP家族探讨睡眠对孕妇糖脂代谢的影响，从生物节律角度对孕妇和子代健康影响提出可能的生物学机制。

本项目依托已建立的广州出生队列研究，持续收集人群数据和血液样本，新增佩戴腕表客观收集以完善睡眠信息，通过建立孕鼠睡眠剥夺模型首次探讨了CTRP 在睡眠质量下降致糖脂代谢紊乱中的作用。. 通过3万余名孕妇数据，项目发现孕妇睡眠质量差、夜间睡眠时间过短及孕妇合并睡眠呼吸紊乱增加了妊娠期糖尿病的发生，我们创新性地根据血糖测定时间点对妊娠期糖尿病进行了三种亚型分类，并首次分析了多项孕妇睡眠指标与妊娠期糖尿病亚型发生的关系，研究发现夜间睡眠时间过短及孕妇合并睡眠呼吸紊乱增加了亚型的发生风险。项目还对孕妇收集了2千余条客观睡眠数据，分析提示妊娠期糖尿病孕妇人群夜间清醒次数更多，白天小觉时间更长，这一发现坚定了无论是客观还是客观睡眠质量差均能增加妊娠期糖尿病的发生风险。项目还建立了孕鼠睡眠剥夺模型，检测了血糖、血脂和CTRP等多种指标，首次探讨了CTRP 在睡眠质量下降致糖脂代谢紊乱中发挥的作用，提示CTRP3、CTRP9在睡眠剥夺导致血脂紊乱过程中起到重要作用，这一系列研究为生物节律与孕期疾病发生提供了可信且珍贵的研究成果。