色素上皮衍生因子在糖尿病视网膜病变中的作用机制研究进展

doi:10.16150/j.1671-2870.2024.02.014

摘要/Abstract

摘要：

糖尿病视网膜病变(diabetic retinopathy, DR)是糖尿病常见的微血管并发症之一，其发病率逐年升高，1980年到2018年发病率为2.2%~12.7%。我国DR发病率为18.45%，全球DR患病率达22.27%。目前，DR已成为全世界成人失明的主要原因，严重影响了糖尿病患者的视网膜正常功能和生活质量。视网膜色素上皮(retinal pigment epithelium, RPE)是视网膜的最外层，对于维持视觉功能至关重要。RPE细胞可分泌色素上皮衍生因子(pigment epithelium-derived factor, PEDF)。PEDF是一种相对分子质量为50 000的天然糖蛋白，属于丝氨酸蛋白酶超家族的一员。现有研究表明，PEDF具有抑制血管生成、抗氧化、抗炎、营养神经等多种生物学活性，对包括DR在内的多种疾病具有保护作用。DR的发病机制较复杂，与氧化应激、炎症反应、线粒体功能障碍、血管内皮生长因子(vascular endothelial growth factor, VEGF)、小胶质细胞异常活化、晚期糖基化终末产物(advanced glycosylation end-pro-duct, AGE)蓄积等有关，其中涉及了Wnt/β-cantenin信号通路、线粒体解偶联蛋白(mitochondrial uncoupling protein, UCP)、核因子κB (nuclear factor-κB, NF-κB)通路、过氧化物酶体增殖物激活受体γ、AGE等。PEDF可以通过这些靶点和通路结合发挥作用，从而阻止DR的发生和进展。本文从PEDF抑制新生血管形成、抗氧化应激、抗炎这3个方面着手，阐述PEDF的不同作用靶点和通路在抑制DR发生、发展中的作用机制，为后期开发可广泛应用于临床的DR治疗新药提供理论依据。

关键词: 色素上皮衍生因子, 糖尿病视网膜病变, 抑制新生血管, 抗氧化应激, 抗炎

Abstract:

Diabetic retinopathy (DR) is one of the most common microvascular complications of diabetes mellitus.The incidence of DR （1980-2018: 2.2%-12.7%） increases year by year. The incidence of DR in China is 18.45%, and global prevalence is 22.27%. DR becomes the leading cause of blindness in adults around the world. DR seriously affects the quality of life of diabetic patients. The retinal pigment epithelium (RPE) is the outermost layer of the retina and is essential for maintaining visual function. RPE cells secrete pigment epithelium-derived factor (PEDF), a natural glycoprotein with a molecular weight of 50 000. PEDF is a member of the serine protease superfamily. Existing studies have demonstrated that PEDF has a wide variety of biological activities, including angiogenesis inhibition, antioxidant, anti-inflammatory, and neurotrophic activities, which have significant effects on a variety of diseases, including DR. The pathogenesis of DR is complex and is related to oxidative stress, inflammatory response, mitochondrial dysfunction, vascular endothelial growth factor (VEGF), abnormal activation of microglia, and accumulation of advanced glycosylation end-products (AGEs), which involves the Wnt/β-cantenin signaling pathway, mitochondrial uncoupling proteins (UCPs), nuclear factor-κB (NF-κB) pathway, peroxisome proliferator-activated receptor γ (PPARγ), AGEs, etc. PEDF may work through these targets and pathways to prevent the occurrence and development of DR. This paper mainly focus on the function of PEDF, including inhibition of neovascularization, anti-oxidative stress and anti-inflammation, and elaborate on the mechanism of PEDF on inhibiting the occurrence and development of DR through different targets and pathways, providing a theoretical basis for the development of new DR therapeutic drugs.

Key words: Pigment epithelium-derived factor, Diabetic retinopathy, Inhibit neovascularization, Antioxidative stress, Anti-inflammation

中图分类号:

周思锋, 朱洁云, 徐海舒, 倪瑛. 色素上皮衍生因子在糖尿病视网膜病变中的作用机制研究进展[J]. 诊断学理论与实践, 2024, 23(02): 192-201.

ZHOU Sifeng, ZHU Jieyun, XU Haishu, NI Ying. Advances in mechanism on pigment epithelium derived factor in diabetes retinopathy[J]. Journal of Diagnostics Concepts & Practice, 2024, 23(02): 192-201.

图/表 3

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