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熊去氧胆酸对高糖下视网膜的保护作用研究及前景
孙佳琪
邹海东 [综述]
作者及单位信息
·
DOI： 10.3760/cma.j.cn115989-20210826-00480
Research and prospects on the protective effect of ursodeoxycholic acid on retina under high glucose
Sun Jiaqi
Zou Haidong
Authors Info & Affiliations
Sun Jiaqi
Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, National Clinical Research Center for Eye Diseases, Shanghai Engineering Research Center of Precise Diagnosis and Treatment of Eye Diseases, Shanghai Key Laboratory of Ocular Fundus Diseases, Shanghai 200080, China
Zou Haidong
Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, National Clinical Research Center for Eye Diseases, Shanghai Engineering Research Center of Precise Diagnosis and Treatment of Eye Diseases, Shanghai Key Laboratory of Ocular Fundus Diseases, Shanghai 200080, China
·
DOI： 10.3760/cma.j.cn115989-20210826-00480
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摘要

糖尿病视网膜病变(DR)是糖尿病的严重微血管并发症之一，可导致视网膜不可逆损伤和严重视力损害。熊去氧胆酸(UDCA)及其衍生物牛磺熊去氧胆酸(TUDCA)作为亲水胆汁酸，具有抗凋亡、抗炎和抗氧化等多重细胞保护作用，近年来在DR的防治研究中展现出潜在的应用前景。本文综述了UDCA/TUDCA在高糖环境下对视网膜神经血管单元的保护作用及其分子机制。研究表明，UDCA/TUDCA能够通过抑制线粒体依赖的细胞凋亡通路、JNK/AP-1信号通路等，保护视网膜神经元免受高糖诱导的损伤；通过抑制内质网应激和减少血管渗漏，维持视网膜血管内皮细胞和周细胞的完整性；通过下调炎症因子表达和抑制小胶质细胞活化，减轻视网膜的炎症反应。此外，UDCA/TUDCA通过结合视网膜细胞上的胆汁酸受体(如TGR5等)，激活相关信号通路，发挥其保护作用。UDCA/TUDCA在DR治疗中展现出广阔的应用前景，未来研究需进一步探索其最佳给药途径和剂量，以期为DR的早期预防和治疗提供新的策略。

糖尿病视网膜病变;熊去氧胆酸;牛磺熊去氧胆酸;视网膜神经血管单元;抗凋亡;抗炎;抗氧化
ABSTRACT

Diabetic retinopathy (DR) is one of the severe microvascular complications of diabetes, which can lead to irreversible retinal damage and significant visual impairment.Ursodeoxycholic acid (UDCA) and its derivative tauroursodeoxycholic acid (TUDCA), as hydrophilic bile acids, exhibit multiple cytoprotective effects including anti-apoptotic, anti-inflammatory, and antioxidant properties and show promising potential in the prevention and treatment of DR.This article reviews the protective effects and molecular mechanisms of UDCA/TUDCA on the retinal neurovascular unit under high glucose conditions.Studies have demonstrated that UDCA/TUDCA protects retinal neurons from high glucose-induced damage by inhibiting mitochondrial-dependent apoptotic pathways and the JNK/AP-1 signaling pathway, maintains the integrity of retinal vascular endothelial cells and pericytes by suppressing endoplasmic reticulum stress and reducing vascular leakage, and alleviates retinal inflammation by downregulating the expression of inflammatory factors and inhibiting microglial activation.Moreover, UDCA/TUDCA exerts its protective effects by binding to bile acid receptors, such as TGR5, on retinal cells and activating related signaling pathways.UDCA/TUDCA holds great potential in the treatment of DR, and future research should focus on optimizing delivery methods and dosages to provide new strategies for the early prevention and treatment of DR.

Diabetic retinopathy;Ursodeoxycholic acid;Tauroursodeoxycholic acid;Retinal neurovascular unit;Anti-apoptosis;Anti-inflammation;Anti-oxidation
Zou Haidong, Email: nc.defudabe.utjsgnodiahuoz
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引用本文

孙佳琪,邹海东. 熊去氧胆酸对高糖下视网膜的保护作用研究及前景[J]. 中华实验眼科杂志,2025,43(03)：271-275.

DOI:10.3760/cma.j.cn115989-20210826-00480

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糖尿病视网膜病变(diabetic retinopathy，DR)是糖尿病常见且较严重的眼部微血管并发症，最终可致盲。世界卫生组织指出，在美国和欧洲，约有15%～17%的盲是由DR造成。DR已成为西方国家工作年龄段人群严重视力丧失的主要原因 [ 1 ]。根据国际糖尿病联盟公布的数据，2019年全球糖尿病患者人数约为4.63亿；糖尿病患者中DR的患病率约为22.27%；2020年DR患病人数约为1.03亿，到2045年将增加至1.61亿 [ 2 ]。DR主要分为非增生性糖尿病视网膜病变(non-proliferative diabetic retinopathy，NPDR)和增生性糖尿病视网膜病变(proliferative diabetic retinopathy，PDR)。目前已知DR与高血糖导致的氧化应激、炎症、晚期糖基化终末产物(advanced glycation end-products，AGEs)积累、细胞因子异常激活、线粒体DNA破坏、周细胞丢失、神经元损伤、血管内皮生长因子(vascular endothelial growth factor，VEGF)表达升高等均相关 [ 3 ]，但具体发病机制尚未完全明确。
DR的治疗手段至今仍较少，除控制血糖、治疗高血压外，玻璃体内注射抗VEGF药物和糖皮质激素类药物已被应用于糖尿病性黄斑水肿的治疗 [ 4 ]；但这些治疗方法对至少一半的患者疗效不明显，且频繁注射给患者的负担较大。对于重度NPDR和PDR，全视网膜激光光凝术或玻璃体手术是主要的治疗手段，但预后均较差 [ 5 ]。因此，寻找安全、低成本的药物来早期预防和控制DR的发生和发展，仍是DR治疗领域重要的研究方向。本文回顾了近期关于熊去氧胆酸(ursodeoxycholic acid，UDCA)及其衍生物牛磺熊去氧胆酸(tauroursodeoxycholic acid，TUDCA)保护高糖下视网膜组织和细胞的相关研究，并探讨其在DR临床应用的前景。
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备注信息
A
邹海东，Email： nc.defudabe.utjsgnodiahuoz
B
所有作者均声明不存在利益冲突
C
国家自然科学基金 (82071012)
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