甘氨酸调控多囊卵巢综合征炎症反应和胰岛素抵抗的作用机制研究

Polycystic ovary syndrome (PCOS) is the most common endocrinological disorder that impairs reproductive health in women. Inflammation and insulin resistance (IR) are main features of disrupted endocrine function in PCOS patients, and are closely associated with reproductive dysfunction and long-term complications. Therefore, identifying the mechanisms of inflammation and IR, establishing effective interventions, and improving pregnancy outcome and long-term reproductive health are of great value to clinical practice. Recent studies have shown that glycine (Gly) inhibits inflammation and improves IR. Our previous metabolomics study demonstrates that, in PCOS patients, plasma Gly level is markedly decreased, and reduced Gly level in follicular fluid is highly correlated with pregnancy failure. Cell biology experiments further indicate that Gly can inhibit the expression of the inflammatory factor IL-6. Based on these findings and combining clinical sample analysis, cell biology experiments and animal models, the current project aims to illustrate the characteristics and molecular mechanisms of Gly in modulating inflammation and IR in PCOS patients. This study will shed new light on the pathogenesis of PCOS, the development of therapeutic targets and the prevention of long-term complications.

多囊卵巢综合征（polycystic ovary syndrome，PCOS）是影响女性生殖健康的最常见的内分泌疾病。其中，炎症和胰岛素抵抗（insulin resistance，IR）是PCOS内分泌紊乱的重要特征，与生殖功能障碍和远期并发症密切相关。因此，明确炎症和IR的发生机制并对其进行有效干预，进而改善妊娠结局和远期健康是临床关注的核心问题。既往研究表明，甘氨酸（glycine，Gly）可抑制炎症反应并可改善IR。本课题组前期代谢组学研究发现，PCOS患者的血浆Gly水平显著降低，且卵泡液中低Gly水平与妊娠失败高度相关；而细胞生物学实验表明，Gly可以抑制炎症因子IL-6的表达。本项目将以前期工作为基础，结合临床样本分析、细胞实验及动物模型，明确Gly调控PCOS炎症反应和IR的特点与分子机制。本研究对于深入理解PCOS发病机理、探索治疗靶点及预防远期并发症具有重要临床意义。

本项目旨在系统探讨甘氨酸调控PCOS患者炎症反应和胰岛素抵抗的作用机制。项目研究工作按照计划执行，研究目标基本实现，通过血浆和卵泡液靶向氨基酸代谢组学分析，明确了甘氨酸与PCOS患者慢性炎症和IR的关系，同时研究发现甘氨酸与支链氨基酸水平显著负相关，且对PCOS患者的胰岛素抵抗和炎症反应有协同调控作用，进一步利用体外颗粒细胞模型，明确甘氨酸通过抑制转录因子NF-kB活性调控PCOS患者炎症反应的分子机制，为临床治疗提供崭新的理论依据和潜在的治疗靶点。此外，进一步拓展PCOS氨基酸代谢研究，揭示了PCOS患者血清中高同型半胱氨酸水平参与PCOS患者胰岛素抵抗和慢性炎症状态的病理过程，并结合蛋白修饰组学方法初步探索PCOS卵巢局部氨基酸代谢异常的翻译后乙酰化修饰调控机制。以上研究结果已发表SCI论文1篇，完成2篇SCI论文撰写、投稿，协助培养2名博士研究生。