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多囊卵巢综合征发病机制中的慢性低度炎症。

Chronic Low Grade Inflammation in Pathogenesis of PCOS.

机构信息

Department of Gynaecological Endocrinology, Medical University of Warsaw, 00-315 Warsaw, Poland.

Department of Dermatology and Venereology, Medical University of Warsaw, 00-315 Warsaw, Poland.

出版信息

Int J Mol Sci. 2021 Apr 6;22(7):3789. doi: 10.3390/ijms22073789.

Abstract

Polycystic ovary syndrome (PCOS) is a one of the most common endocrine disorders, with a prevalence rate of 5-10% in reproductive aged women. It's characterized by (1) chronic anovulation, (2) biochemical and/or clinical hyperandrogenism, and (3) polycystic ovarian morphology. PCOS has significant clinical implications and can lead to health problems related to the accumulation of adipose tissue, such as obesity, insulin resistance, metabolic syndrome, and type 2 diabetes. There is also evidence that PCOS patients are at higher risk of cardiovascular diseases, atherosclerosis, and high blood pressure. Several studies have reported the association between polycystic ovary syndrome (PCOS) and low-grade chronic inflammation. According to known data, inflammatory markers or their gene markers are higher in PCOS patients. Correlations have been found between increased levels of C-reactive protein (CRP), interleukin 18 (IL-18), tumor necrosis factor (TNF-α), interleukin 6 (IL-6), white blood cell count (WBC), monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-1α (MIP-1α) in the PCOS women compared with age- and BMI-matched controls. Women with PCOS present also elevated levels of AGEs and increased RAGE (receptor for advanced glycation end products) expression. This chronic inflammatory state is aggravating by obesity and hyperinsulinemia. There are studies describing mutual impact of hyperinsulinemia and obesity, hyperandrogenism, and inflammatory state. Endothelial cell dysfunction may be also triggered by inflammatory cytokines. Many factors involved in oxidative stress, inflammation, and thrombosis were proposed as cardiovascular risk markers showing the endothelial cell damage in PCOS. Those markers include asymmetric dimethylarginine (ADMA), C-reactive protein (CRP), homocysteine, plasminogen activator inhibitor-I (PAI-I), PAI-I activity, vascular endothelial growth factor (VEGF) etc. It was also proposed that the uterine hyperinflammatory state in polycystic ovary syndrome may be responsible for significant pregnancy complications ranging from miscarriage to placental insufficiency. In this review, we discuss the most importance evidence concerning the role of the process of chronic inflammation in pathogenesis of PCOS.

摘要

多囊卵巢综合征(PCOS)是最常见的内分泌疾病之一,在育龄妇女中的患病率为 5-10%。其特征为(1)慢性无排卵,(2)生化和/或临床高雄激素血症,以及(3)多囊卵巢形态。PCOS 具有重要的临床意义,可导致与脂肪组织堆积相关的健康问题,如肥胖、胰岛素抵抗、代谢综合征和 2 型糖尿病。还有证据表明,PCOS 患者患心血管疾病、动脉粥样硬化和高血压的风险更高。几项研究报告了多囊卵巢综合征(PCOS)与低度慢性炎症之间的关联。根据已知数据,PCOS 患者的炎症标志物或其基因标志物水平较高。已经发现 C 反应蛋白(CRP)、白细胞介素 18(IL-18)、肿瘤坏死因子(TNF-α)、白细胞介素 6(IL-6)、白细胞计数(WBC)、单核细胞趋化蛋白-1(MCP-1)和巨噬细胞炎性蛋白-1α(MIP-1α)在 PCOS 女性中与年龄和 BMI 匹配的对照组相比,水平升高。患有 PCOS 的女性还表现出 AGEs 水平升高和 RAGE(晚期糖基化终产物受体)表达增加。这种慢性炎症状态会因肥胖和高胰岛素血症而加重。有研究描述了高胰岛素血症和肥胖、高雄激素血症和炎症状态之间的相互影响。内皮细胞功能障碍也可能由炎症细胞因子触发。许多涉及氧化应激、炎症和血栓形成的因素被提议作为心血管风险标志物,表明 PCOS 中的内皮细胞损伤。这些标志物包括不对称二甲基精氨酸(ADMA)、C 反应蛋白(CRP)、同型半胱氨酸、纤溶酶原激活物抑制剂-1(PAI-1)、PAI-1 活性、血管内皮生长因子(VEGF)等。还提出多囊卵巢综合征中子宫的过度炎症状态可能导致从流产到胎盘功能不全等重大妊娠并发症。在这篇综述中,我们讨论了慢性炎症过程在 PCOS 发病机制中的作用的最重要证据。

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