非肥胖型多囊卵巢综合征合并复发性流产患者血浆代谢特征研究

Plasma Metabolic Characteristics in Non-Obese Polycystic Ovary Syndrome Patients with Recurrent Spontaneous Abortion

摘要: 目的：本研究通过非靶向代谢组学技术聚焦非肥胖型多囊卵巢综合征合并复发性流产患者(PCOS-RSA)的代谢紊乱机制。对小分子代谢物进行定量分析，数据经过主成分分析、正交偏最小二乘法分析、聚类热图分析、火山图分析、代谢通路分析从而找到与该疾病相关的生物标志物和代谢途径，揭示其中的分子机制。方法：严格筛选BMI < 24 kg/m²的非肥胖PCOS-RSA患者28例(2024~2025年于包钢三医院就诊的非肥胖型PCOS-RSA患者)。15例健康患者做对照组，采用Agilent 1290 Infinity LC超高效液相色谱系统色谱柱进行血浆的分离，Triple TOF 6600质谱仪(AB SCIEX)检测，最后经过数据转换后筛选出差异代谢物及关联基因。结果：共鉴定了1718个代谢物 ，二级鉴定代谢物1500个，筛出430个差异代谢物(上调274、下调156)，核心差异物包括：根皮苷、苦杏仁苷、色氨酸–谷氨酸–组氨酸、5-雄甾-3-醇-17-酮硫酸盐 、地鲁波酮、11-脱氢血栓烷B3、琥珀酸、16α-雌三醇-β-D-葡萄糖醛。结论：非肥胖亚型以神经内分泌失调为主导(如5-雄甾醇硫酸盐↓86%)。非肥胖型PCOS-RSA的核心病理机制是代谢紊乱构成的恶性循环：脂质炎症→胰岛素抵抗→Hcy升高→氧化应激→卵母细胞质量下降。通过靶向调控血浆关键代谢物(如应用GABA受体激动剂抑制色氨酸–谷氨酸–组氨酸三肽、抑制11-脱氢血栓烷B3上调等)，可打破这一循环，明显改善流产结局。未来有望建立基于代谢表型的非肥胖型PCOS-RSA分型诊疗体系，实现精准干预。

Abstract: This study focuses on the metabolic disorder mechanisms in non-obese patients with polycystic ovary syndrome complicated by recurrent spontaneous abortion (PCOS-RSA) using untargeted metabolomics techniques. Quantitative analysis of small-molecule metabolites was performed, and data were subjected to principal component analysis, orthogonal partial least squares analysis, cluster heatmap analysis, volcano plot analysis, and metabolic pathway analysis to identify disease-related biomarkers and metabolic pathways, thereby revealing the underlying molecular mechanisms. Methods: A total of 28 non-obese PCOS-RSA patients with BMI < 24 kg/m² were strictly selected (non-obese PCOS-RSA patients treated at the Third Hospital of Baotou Steel from 2024 to 2025). Fifteen healthy individuals served as the control group. Plasma samples were separated using an Agilent 1290 Infinity LC ultra-high-performance liquid chromatography system, and detected by a Triple TOF 6600 mass spectrometer (AB SCIEX). After data transformation, differential metabolites and associated genes were screened. Results: A total of 1718 metabolites were identified, including 1500 metabolites with secondary identification. Among them, 430 differential metabolites were screened out (274 upregulated and 156 downregulated). Core differential metabolites included phlorizin, amygdalin, tryptophan-glutamate-histidine, 5-androstene-3-ol-17-one sulfate, delu, 11-dehydrothromboxane B3, succinic acid, and 16α-estriol-β-D-glucuronide. Conclusion: Neuroendocrine dysregulation dominates the non-obese subtype (e.g., 5-androstenol sulfate decreased by 86%). The core pathological mechanism of non-obese PCOS-RSA is a vicious cycle of metabolic disorders: lipid inflammation → insulin resistance → elevated homocysteine (Hcy) → oxidative stress → decreased oocyte quality. Targeted regulation of key plasma metabolites (e.g., using GABA receptor agonists to inhibit the tryptophan-glutamate-histidine tripeptide, or suppressing the upregulation of 11-dehydrothromboxane B3) can break this cycle and significantly improve abortion outcomes. In the future, it is expected to establish a metabolic phenotype-based classification, diagnosis, and treatment system for non-obese PCOS-RSA to achieve precise intervention.