目的: 探讨甘氨酸与多囊卵巢综合征（polycystic ovary syndrome,PCOS）发病机制的关联。方法: 检测11名PCOS患者和11名正常对照组女性血清甘氨酸（glycine,Gly）水平,并与临床资料行相关性分析。构建小鼠模型,分为对照组（Ctrl）组,Gly组,PCOS 组和PCOS+Gly组。观察各组小鼠动情周期变化和卵巢形态,检测脂质代谢指标和性激素指标,RT qPCR法检测卵巢组织性激素受体及激素合成酶的表达。结果: PCOS组患者体内血清甘氨酸水平较Ctrl组女性降低,其血清游离雄激素指数（free androgen index ,FAI）、黄体生成素（luteinizing hormone,LH）、LH/促卵泡生成素（follicle-stimulating Hormone,FSH）水平显著高于Ctrl组,性激素结合球蛋白（sex hormone binding globulin,SHBG）水平显著低于Ctrl组。在总样本人群中,甘氨酸水平与SHBG呈正相关,与FAI和LH/FSH呈负相关。甘氨酸减轻了PCOS小鼠体重,降低了总胆固醇和低密度脂蛋白水平。加快了PCOS小鼠动情周期的恢复,减少了卵巢囊状卵泡和出血性囊肿数量,卵巢组织中CYP17A1、CYP19A1、FSHR和LHR的mRNA水平的 mRNA 水平明显下调。结论: 总人群血清甘氨酸水平与SHBG呈正相关,与FAI、LH/FSH 比值呈负相关;PCOS患者存在甘氨酸减少现象。甘氨酸可改善PCOS小鼠的脂质代谢紊乱,恢复正常动情周期,保护卵巢正常形态并调控性激素水平,甘氨酸可能通过调控性激素合成相关基因表达抑制PCOS 的发生发展。
Abstract
Objective To investigate the association between glycine and the pathogenesis of PCOS. Methods Glycine levels were detected and correlation analysis was performed in 11 PCOS patients and 11 healthy women. Mouse models were constructed and divided into Ctrl group, Gly group, PCOS group, and PCOS+Gly group. Estrous cycle and ovarian morphology were observed. Sex hormone and lipid metabolism indicators were detected. RT qPCR was used to detect the mRNA levels of hormone synthase and sex hormone receptor in ovarian tissues. Results (1) Serum glycine levels in PCOS patients were decreased compared to the control group and the values of FAI, LH and LH/FSH levels in PCOS patients were increased, while SHBG were decreased. In the total sample population, glycine levels were positively correlated with SHBG and negatively correlated with FAI and LH/FSH ratio. Glycine reduced body weight and TC and LDL-C levels of PCOS mice. It also accelerated the recovery of estrus cycle, reduced the number of cystic follicles and hemorrhagic cysts, and downregulated the mRNA levels of CYP17A1, CYP19A1, FSHR, and LHR. Conclusion Serum glycine levels were positively correlated with SHBG, and negatively correlated with FAI and LH/FSH ratio. PCOS patients exhibited a decrease in glycine levels. Glycine improved the disorder of lipid metabolism in PCOS mice, restored normal estrus cycle, protected normal ovarian morphology and regulated sex hormone levels. Glycine may inhibit the occurrence and development of PCOS by regulating the expression of genes related to hormone synthesis.
关键词
甘氨酸 /
多囊卵巢综合征 /
动情周期 /
性激素 /
性激素受体
Key words
glycine /
polycystic ovary syndrome /
estrous cycle /
sex hormone /
sex hormone receptor
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基金
国家自然科学基金面上项目“circPVT1调控miR-125b/PaK3在PCOS高雄激素血症中作用机制研究”（81873820）; 江苏省卫生健康委员会2023年度医学科研面上项目“己酸介导组蛋白乙酰化调控Th17/IL17A 在肥胖型 PCOS 中的作用及机制研究”（H2023113）
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