多囊卵巢综合征(polycystic ovary syndrome，PCOS)是一种常见的生殖内分泌疾病，主要表现为排卵障碍、月经周期紊乱和高雄激素血症等，常伴有胰岛素抵抗、肥胖和代谢异常。PCOS发病机制涉及遗传因素、环境因素、慢性炎症和自身免疫等多个方面。二甲双胍是一种AMP活化蛋白激酶(AMP-activated protein kinase，AMPK)激活剂，能够增强胰岛素敏感性并降低AMPK-环磷酸腺苷(cyclic adenosine monophosphate，cAMP)活性水平，进而抑制糖异生酶的表达。近期研究发现二甲双胍可以通过缓解慢性炎症、抵抗氧化应激、恢复线粒体功能、抑制铁死亡等诸多途径促进卵泡发育和成熟，改善胰岛素抵抗，恢复月经周期。此外，二甲双胍激活AMPK与降低PCOS患者心血管疾病风险及减轻肝功能损伤有关。综述二甲双胍激活AMPK在治疗PCOS中的作用机制。
New Progress in the Mechanism of Metformin Therapy for Polycystic Ovary Syndrome
Polycystic ovary syndrome(PCOS)is a common reproductive endocrine disease,mainly manifested by ovulation disorders,menstrual cycle disorders,hyperandrogenemia,etc.,and often accompanied by insulin resistance,obesity and metabolic abnormalities.The pathogenesis of PCOS involves genetic factors,environmental factors,chronic inflammation,autoimmune and so on.Metformin as an AMP-activated protein kinase(AMPK)activator can enhance insulin sensitivity and decrease AMPK-cyclic adenosine monophosphate(cAMP),and thereby reduce the expression of gluconogenic enzymes.Metformin can promote follicle development and maturation,improve insulin resistance and restore the menstrual cycle,by relieving chronic inflammation,resisting oxidative stress,restoring mitochondrial function,inhibiting ferroptosis,and many other aspects.In addition,the activation of AMPK by metformin is closely related to the reduced risk of cardiovascular disease and the alleviation of liver damage in PCOS patients.The mechanism of AMPK activated by metformin in the treatment of PCOS was reviewed in this paper.
Polycystic ovary syndromeMetforminAMP-activated protein kinasesTherapy
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