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多囊卵巢综合征(PCOS)是一种育龄女性常见的内分泌及代谢功能失调性疾病,其主要临床特征表现为排卵功能障碍、高雄激素血症以及卵巢多囊性改变。缺氧诱导因子-1α(HIF-1α)作为细胞在缺氧环境下应答的关键性转录调节因子,可能参与了PCOS发病进展过程。本文从卵巢功能障碍、胰岛素抵抗、代谢异常以及慢性炎症等多个方面,来详细阐述HIF-1α在PCOS发病与进展中的潜在作用机制,以期为PCOS的临床治疗提供科学的理论依据。
Abstract:Polycystic ovary syndrome(PCOS)is a common endocrine and metabolic disorder in women of childbearing age.Its main characteristics are ovulatory dysfunction,hyperandrogenemia and ovarian polycystic changes.Hypoxia inducible factor-1α(HIF-1α),as a key transcriptional regulator of cellular response under hypoxia,may be involved in the progression of PCOS.This article aims to elaborate the potential mechanism of HIF-1αin the onset and development of PCOS by discussing ovarian dysfunction,insulin resistance,metabolic abnormalities and chronic inflammation,so as to provide a scientific theoretical basis for the clinical treatment of PCOS.
[1] Salari N,Nankali A,Ghanbari A,et al.Global prevalence of poly cystic ovary syndrome in women worldwide:a comprehensive systematic review and meta-analysis[J].Arch Gynecol Obstet,2024,310:1303-1314.
[2] Sadeghi HM,Adeli I,Calina D,et al. Polycystic ovary syndrome:a comprehensive review of pathogenesis,management,and drug interposing[J].Int J Mol Sci,2022,23:583.
[3] ZSánchez-Garrido MA,Serrano-López V,Ruiz-Pino F,et al.Superior metabolic improvement of polycystic ovary syndrome traits after GLP1-based multi-agonist therapy[J]. Nat Commun,2024,15:8498.
[4] Ruan H,Zhang Q,Zhang YP,et al.Unraveling the role of HIF-1α in sepsis:from pathophysiology to potential therapeutics-a narrative review[J].Crit Care,2024,28:100.
[5] Fu X,Shi L,Liu P,et al.Expression and clinical significance of HIF-1αin Follicular fluid and granulosa cells in infertile PCOS patients[J].Reprod Sci,2023,30:2263-2274.
[6]中华预防医学会生育力保护分会生殖内分泌生育保护学组.多囊卵巢综合征合并胰岛素抵抗诊治专家共识[J].生殖医学杂志,2024,33:1133-1140.
[7] Sim J,Cowburn AS,Palazon A,et al.The factor inhibiting HIF asparaginyl hydroxylase regulates oxidative metabolism and accelerates metabolic adaptation to hypoxia[J].Cell Metab,2018,27:898-913.e7.
[8] Luo Z,Tian M,Yang G,et al.Hypoxia signaling in human health and diseases:implications and prospects for therapeutics[J].Signal Transduct Target Ther,2022,7:218.
[9]李蓓,王路瑶,唐轶珣,等.HIF-1α在新生儿缺血缺氧性脑病中的研究进展[J].中南医学科学杂志,2023,51:309-312.
[10]陈欢欢,张磊,张珊,等.自噬在多囊卵巢综合征中的调控作用研究[J].生殖医学杂志,2023,32:138-143.
[11]王美玲,刘华绪.HIF-VEGF-Notch信号通路在血管生成中的作用[J].中国麻风皮肤病杂志,2021,37:332-336.
[12] Chen Z,Han F,Du Y,et al.Hypoxic microenvironment in cancer:molecular mechanisms and therapeutic interventions[J].Signal Transduct Target Ther,2023,8:70.
[13] Tang Z,Zhang Z,Lin Q,et al. HIF-1α/BNIP3-mediated autophagy contributes to the luteinization of granulosa cells during the formation of corpus luteum[J].Front Cell Dev Biol,2021,8:619924.
[14] Wang F,Han J,Wang X,et al.Roles of HIF-1α/BNIP3mediated mitophagy in mitochondrial dysfunction of letrozoleinduced PCOS rats[J].J Mol Histol,2022,53:833-842.
[15] Wang J,Wu X.The effects of mitochondrial dysfunction on energy metabolism switch by HIF-1αsignal in granular cells of poly cystic ovary syndrome[J].Endokrynol Pol,2020,71:134-145.
[16] Wang Y,Wang Y,Chen Y,et al.HDAC5inhibits ovarian angiogenesis in dehydroepiandrosterone-induced mouse model of polycystic ovary syndrome[J].Folia Histochem Cytobiol,2022,60:260-270.
[17] Patil K,Hinduja I,Mukherjee S.Alteration in angiogenic potential of granulosa-lutein cells and follicular fluid contributes to luteal defects in polycystic ovary syndrome[J].Hum Reprod,2021,36:1052-1064.
[18] Cao LY,Zhang ZQ,Liu PP,et al.Aberrant BMP15/HIF-1α/SCF signaling pathway in human granulosa cells is involved in the PCOS related abnormal follicular development[J].Gynecol Endocrinol,2022,38:971-977.
[19] Szymanska M,Shrestha K,Girsh E,et al.Reduced endothelin-2and hypoxic signaling pathways in granulosa-lutein cells of PCOS women[J].Int J Mol Sci,2021,22:8216.
[20] Lee SH,Park SY,Choi CS. Insulin resistance:from mechanisms to therapeutic strategies[J].Diabetes Metab J,2022,46:15-37.
[21] Zhao H,Zhang J,Cheng X,et al.Insulin resistance in poly cystic ovary syndrome across various tissues:an updated review of pathogenesis,evaluation,and treatment[J].J Ovarian Res,2023,16:9.
[22]包宇航,苏红,郑仁东.性激素结合球蛋白参与糖尿病发生发展的研究进展[J].中国基层医药,2023,30:1112-1115.
[23] Huang R,Wang Y,Yan R,et al.Sex hormone binding globulin is an independent predictor for insulin resistance in male patients with newly diagnosed type 2diabetes mellitus[J].Diabetes Ther,2023,14:1627-1637.
[24] Xing C,Li C,He B.Insulin sensitizers for improving the endocrine and metabolic profile in overweight women with PCOS[J].J Clin Endocrinol Metab,2020,105:2950-2963.
[25]王洋,金钧,王国华.多囊卵巢综合征游离脂肪酸水平与胰岛素抵抗的相关性[J].中国妇产科临床杂志,2020,21:600-602.
[26] Lemaitre M,Christin-Maitre S,Kerlan V.Polycystic ovary syndrome and adipose tissue[J].Ann Endocrinol(Paris),2023,84:308-315.
[27] Tong C,Wu Y,Zhang L,et al.Insulin resistance,autophagy and apoptosis in patients with polycystic ovary syndrome:Association with PI3K signaling pathway[J]. Front Endocrinol(Lausanne),2022,13:1091147.
[28] Murri M,Luque-Ramírez M,Insenser M,et al.Circulating markers of oxidative stress and polycystic ovary syndrome(PCOS):a systematic review and meta-analysis[J].Hum Reprod Update,2013,19:268-288.
[29] Yu J,Zhou Y,Ding J,et al.Characteristics and possible mechanisms of metabolic disorder in overweight women with polycystic ovary syndrome[J].Front Endocrinol(Lausanne),2023,13:970733.
[30] LaPoint A,Singer JM,Ferguson D,et al.Adipocyte lipin 1expression associates with human metabolic health and regulates systemic metabolism in mice[J].J Clin Invest,2024,134:e169722.
[31] He Y,Yang W,Gan L,et al.Silencing HIF-1αaggravates non-alcoholic fatty liver disease in vitro through inhibiting PPAR-α/ANGPTL4 singling pathway[J]. Gastroenterol Hepatol,2021,44:355-365.
[32] Guo F,Xu S,Zhu Y,et al.PPARγtranscription deficiency exacerbates high-fat diet-induced adipocyte hypertrophy and insulin resistance in mice[J].Front Pharmacol,2020,11:1285.
[33] Wei LY,Lin YW,Luo JC,et al. Design,synthesis and structure-activity relationship of novel 2-pyrimidinylindole derivatives as orally available anti-obesity agents[J].Eur J Med Chem,2024,277:116773.
[34] Luo M,Li T,Sang H.The role of hypoxia-conductible factor1αin hepatic lipid metabolism[J].J Mol Med(Berl),2023,101:487-500.
[35] Poblete JMS,Ballinger MN,Bao S,et al.Macrophage HIF-1αmediates obesity-related adipose tissue dysfunction via interleukin-1receptor-associated kinase M[J].Am J Physiol Endocrinol Metab,2020,318:E689-E700.
[36] Aemanini D,Boscaro M,Bordin L,et al.Controversies in the pathogenesis,diagnosis and treatment of PCOS:focus on insulin resistance,inflammation,and hyperparathyroidism[J].Int J Mol Sci,2022,23:4110.
[37] Yang P,Feng J,Peng Q,et al.Advanced glaciation end products:potential mechanism and therapeutic target in cardiovascular complications under diabetes[J].Oxid Med Cell Longev,2019,2019:9570616.
[38]张步春,张甜甜,项楚涵,等.木犀草素通过HIF-1α抑制糖酵解调控M1型巨噬细胞极化[J].中国药理学通报,2023,39:244-251.
[39] Brand KM,Gottwald-Hostalek U,Andag-Silva A.Update on the therapeutic role of metformin in the management of polycystic ovary syndrome:Effects on pathophysiologic process and fertility outcomes[J].Womens Health(Lond),2025,21:17455057241311759.
[40] Wang G,Mao W,Zhang Y,et al.Multiomics and systematic analyses reveal the roles of hemoglobin and the HIF-1pathway in polycystic ovary syndrome[J].Adv Sci(Weinh),2025,14:e2411679.
[41] Zhang R,Xu W,Wei H,et al. Mechanism of YJKL decoration in treating of PCOS infertility by integrative approach of network pharmacology and experimental verification[J].Drug Des Devel Ther,2024,18:3853-3870.
[42] Bahramrezaie M,Amidi F,Aleyasin A,et al. Effects of restorative on VEGF&HIF1genes expression in granular cells in the pathogenesis pathway and laboratory parameters of poly cystic ovary syndrome:a triple-blind randomized clinical trial[J].J Assist Reprod Genet,2019,36:1701-1712.
基本信息:
中图分类号:R711.75
引用信息:
[1]潘丽媛,刘唱,陈琳,等.缺氧诱导因子-1α在PCOS发病机制中的研究进展[J].生殖医学杂志,2025,34(09):1284-1289.
基金信息:
吴阶平基金会临床科研专项资助基金(320.6750.18542)
2025-09-15
2025-09-15