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论文题名(中文):

 妊娠期维生素 K2营养状况评估方法探究    

姓名:

 王瑞    

论文语种:

 chi    

学位:

 硕士    

学位类型:

 学术学位    

学校:

 北京协和医学院    

院系:

 北京协和医学院北京协和医院    

专业:

 公共卫生与预防医学-营养与食品卫生学    

指导教师姓名:

 刘燕萍    

论文完成日期:

 2025-04-23    

论文题名(外文):

 Investigation of Assessment Methods for Vitamin K2 Nutritional Status During Pregnancy    

关键词(中文):

 维生素 K2 妊娠期 营养评价 骨代谢 脂质组学    

关键词(外文):

 Vitamin K2 Pregnancy Nutritional assessment Bone metabolism Lipidomics    

论文文摘(中文):

目的 维生素 K2 VK2,甲基萘醌类)作为重要的脂溶性维生素,在妊娠期代谢健 康中起关键作用,其营养状况评估方法尚未明确。本研究旨在探讨妊娠期 VK2 的 营养状况评估方法,分析循环 VK2 水平与基线资料以及妊娠期并发症的关系, 阐明其与骨代谢及脂质代谢的关联,并验证甘油三酯 TG)作为 VK2 水平校正 指标的可行性。 方法 本研究采用横断面设计,共纳入 199 名妊娠期女性,检测血清 VK1、VK2 MK4、 MK7)水平、骨代谢标志物 OST、PINP、β-CTx)及脂质组。通过液相色谱-质 谱联用技术 LC-MS/MS)测定 VK2 亚型,采用限制性立方样条模型分析 VK2 水平与骨代谢指标的非线性关系,采用脂质组学分析其与脂质代谢物的相关性, 并最终评估 TG 对 VK2 水平的校正效果。 结果 妊娠期循环 VK1、VK2水平随妊娠期进展逐渐显著升高,其中 MK4 和 MK7 呈现不同的代谢特征。在校正孕周和年龄后 MK7 与产次 OR=1.348,P=0.005)、 Apgar 评分 1 分钟 OR=-0.040, P=0.043)和早产 OR=1.459, P=0.047)的发 生显著相关。与骨代谢的相关性分析显示,MK7 与骨形成标志物 OST、PINP) 和骨吸收标志物 β-CTx)均呈显著正相关,而 MK4 仅与 β-CTx 显著相关。限 制性立方样条分析表明,骨代谢指标在 MK7 达到 7ng/ml 时趋于稳定,提示 MK7 在妊娠期骨代谢调控中起更广泛作用。脂质组学分析发现,VK1、MK7 和 MK4 与甘油脂类 GL)、甘油磷脂类 GP)呈正相关,而与游离脂肪酸 FA)呈负相 关,且这一趋势与妊娠期脂质代谢变化一致。TG 与 VK2 亚型 尤其是 MK7)显 著相关,支持其作为 VK2 校正指标的适用性。对这一结论进行临床数据验证显 示,各亚型 VK 血清水平均与 TG 相关性显著,另外在使用 TG 校正后的 VK 水 平与其他代谢物的相关性分析能够消除血脂带来的影响。 结论 5 本研究系统揭示了妊娠期 VK2 亚型的差异化代谢特征及其与骨代谢、脂质代 谢的复杂关联。相比于 MK4,MK7 在妊娠并发症的发生和骨代谢调控中作用更 为广泛,而 TG 可作为妊娠期 VK2 营养状况的校正指标。研究结果为妊娠期 VK2 营养状态评估提供了新的理论依据。

论文文摘(外文):

Objective Vitamin K2 (VK2), a group of menaquinones, is a fat-soluble vitamin that plays a critical role in metabolic health during pregnancy. However, methods for evaluating VK2 nutritional status in this context remain unclear. This study aims to explore assessment methods for VK2 nutritional status in pregnant women, investigate the association between circulating VK2 levels and baseline characteristics as well as pregnancy complications, elucidate the relationship between VK2 and bone and lipid metabolism, and evaluate the feasibility of using triglycerides (TG) as a correction index for VK2 levels. Methods This cross-sectional study enrolled a cohort of 199 pregnant women. Serum levels of VK1, VK2 subtypes (MK4 and MK7), bone turnover markers (OST, PINP, βCTx), and lipidomic profiles were measured. VK2 subtypes were quantified using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Restricted cubic spline models were applied to assess nonlinear associations between VK2 levels and bone metabolism markers. Lipidomics was employed to explore correlations with lipid metabolites, and the effectiveness of TG as a correction factor for VK2 levels was evaluated. Results Circulating levels of VK1 and VK2 increased significantly as pregnancy progressed, with MK4 and MK7 exhibiting distinct metabolic profiles. After adjusting 6 for gestational age and maternal age, MK7 levels were significantly associated with parity (OR = 1.348, P = 0.005), 1-minute Apgar score (OR = -0.040, P = 0.043), and preterm birth (OR = 1.459, P = 0.047). MK7 showed significant positive correlations with both bone formation markers (OST, PINP) and bone resorption marker (β-CTx), while MK4 was only significantly associated with β-CTx. Restricted cubic spline analysis indicated that bone metabolic markers plateaued when MK7 levels reached approximately 7 ng/mL, suggesting a broader regulatory role of MK7 in bone metabolism during pregnancy. Lipidomic analysis revealed that VK1, MK7, and MK4 were positively correlated with glycerolipids (GL) and glycerophospholipids (GP), but negatively correlated with free fatty acids (FA), a trend consistent with lipid metabolic changes in pregnancy. TG was significantly correlated with VK2 subtypes, particularly MK7, supporting its use as a correction factor. Clinical validation confirmed strong associations between serum VK subtypes and TG levels, and adjustment using TG effectively reduced lipid-induced variation in correlation analyses with other metabolites. Conclusion This study systematically elucidates the differential metabolic characteristics of VK2 subtypes during pregnancy and their complex associations with bone and lipid metabolism. Compared to MK4, MK7 exhibits broader involvement in pregnancy-related complications and bone metabolic regulation. TG is a feasible correction index for assessing VK2 nutritional status during pregnancy. These findings provide novel theoretical insights for the evaluation of VK2 status in pregnant populations. 

开放日期:

 2025-06-09    

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