硫氧还蛋白相互作用蛋白在多囊卵巢综合征中作用的研究进展

doi:10.12280/gjfckx.20220603

摘要/Abstract

摘要：

多囊卵巢综合征（polycystic ovary syndrome，PCOS）是一种常见于育龄妇女的内分泌代谢性疾病，以月经不规则、高雄激素血症和卵巢多囊样改变为特征，常表现为肥胖、不孕和胰岛素抵抗。硫氧还蛋白相互作用蛋白（thioredoxin-interacting protein，TXNIP）是一种多功能调节剂，不仅参与胰岛素分泌和葡萄糖代谢的调节，还与氧化应激、炎症因子和情绪障碍密切相关。PCOS患者体内的TXNIP水平较健康人群明显增加，表明TXNIP可能参与PCOS及其并发症的发生、发展。近年体内外研究尝试应用中药提取物和西医药物抑制TXNIP的表达，TXNIP特异性抑制剂的发现使TXNIP有望成为抑制PCOS进程的有效靶点。综述TXNIP在PCOS中的作用进展，以期为PCOS发病机制的深入研究及临床诊疗提供新的思路和方向。

关键词: 硫氧还蛋白相互作用蛋白, 多囊卵巢综合征, 胰岛素抗药性, 炎症, 代谢, 治疗

Abstract:

Polycystic ovary syndrome (PCOS) is an endocrine and metabolic disease commonly in women of reproductive age, characterized by irregular menstruation, hyperandrogenemia and polycystic ovary changes, often manifested as obesity, infertility and insulin resistance. Thioredoxin-interacting protein (TXNIP) is a multifunctional regulator that is not only involved in the regulation of insulin secretion and glucose metabolism, but also closely related to oxidative stress, inflammatory factors and mood disorders. Studies have shown that TXNIP levels are significantly increased in PCOS patients, suggesting that TXNIP may be involved in the development of PCOS and its complications. In recent years, some in vivo and ex vivo studies have attempted to use herbal extracts and western drugs to inhibit TXNIP expression, and the discovery of TXNIP-specific inhibitors makes it a promising and effective target to inhibit the process of PCOS. This article reviews the role of TXNIP in PCOS, in order to provide new ideas and directions for the in-depth study of PCOS pathogenesis and its clinical diagnosis and treatment.

Key words: Thioredoxin-interacting protein, Polycystic ovary syndrome, Insulin resistance, Inflammatory, Metabolism

叶莎, 黄烨佩, 马林, 包晓燕, 杨茹, 邓妙, 黄坚. 硫氧还蛋白相互作用蛋白在多囊卵巢综合征中作用的研究进展[J]. 国际妇产科学杂志, 2022, 49(6): 708-712.

YE Sha, HUANG Ye-pei, MA Lin, BAO Xiao-yan, YANG Ru, DENG Miao, HUANG Jian. Research Progress on the Role of Thioredoxin-Interacting Protein in Polycystic Ovary Syndrome[J]. Journal of International Obstetrics and Gynecology, 2022, 49(6): 708-712.

图/表 1

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	药物名称	研究对象	主要机制
中药提取物	红景天苷	T2DM小鼠^[23]；HFD诱导的NASH小鼠^[24]	通过TXNIP/NLRP3炎症小体通路减轻氧化应激；减少肝脏中的脂质堆积
机制	黄连素	MCD诱导的NASH小鼠^[25]	同上
	槲皮素	STZ诱导的DM大鼠^[26]；HFD诱导的NASH大鼠^[27]	同上
	京尼平苷	脂肪细胞^[18]；胰岛细胞瘤细胞^[28]	增强葡萄糖摄取，增加IRS-1和GLUT-1的蛋白质水平；通过蛋白酶体途径加速TXNIP降解，改善胰岛素信号传导缺陷
	Icariin	高糖诱导的C2C12肌管细胞^[29]	通过蛋白酶体依赖性机制改善IR；抑制内质网应激
西药	维拉帕米	STZ诱导的DM小鼠^[30]；T2DM患者^[31]	减少细胞内钙，抑制钙调磷酸酶信号传导；减少ChREBP与TXNIP启动子中E-box重复序列的结合
	二甲双胍	APOE^-/-小鼠^[32]	激活AMPK，调控TRX/TXNIP复合物；抑制NLRP3炎症小体的激活
	维生素D	高葡萄糖培养的人内皮细胞^[33]	阻碍HUVECs中的脂滴形成，纠正HUVEC中的脂质代谢失衡
	度拉鲁肽	内皮细胞^[34]	抑制ROS的产生，降低NLRP3炎症小体和caspase-1的表达

	药物名称	研究对象	主要机制
中药提取物	红景天苷	T2DM小鼠^[23]；HFD诱导的NASH小鼠^[24]	通过TXNIP/NLRP3炎症小体通路减轻氧化应激；减少肝脏中的脂质堆积
机制	黄连素	MCD诱导的NASH小鼠^[25]	同上
	槲皮素	STZ诱导的DM大鼠^[26]；HFD诱导的NASH大鼠^[27]	同上
	京尼平苷	脂肪细胞^[18]；胰岛细胞瘤细胞^[28]	增强葡萄糖摄取，增加IRS-1和GLUT-1的蛋白质水平；通过蛋白酶体途径加速TXNIP降解，改善胰岛素信号传导缺陷
	Icariin	高糖诱导的C2C12肌管细胞^[29]	通过蛋白酶体依赖性机制改善IR；抑制内质网应激
西药	维拉帕米	STZ诱导的DM小鼠^[30]；T2DM患者^[31]	减少细胞内钙，抑制钙调磷酸酶信号传导；减少ChREBP与TXNIP启动子中E-box重复序列的结合
	二甲双胍	APOE^-/-小鼠^[32]	激活AMPK，调控TRX/TXNIP复合物；抑制NLRP3炎症小体的激活
	维生素D	高葡萄糖培养的人内皮细胞^[33]	阻碍HUVECs中的脂滴形成，纠正HUVEC中的脂质代谢失衡
	度拉鲁肽	内皮细胞^[34]	抑制ROS的产生，降低NLRP3炎症小体和caspase-1的表达