背景:牛磺熊去氧胆酸(TUDCA)是一种天然产生的亲水性胆汁酸,已在中药中使用了数百年。许多最近的体外和体内研究表明,TUDCA在各种视网膜疾病模型中具有神经保护作用。
目的:系统回顾科学文献,全面总结TUDCA的神经保护作用和细胞保护作用机制。
方法:按照PRISMA(系统评价和荟萃分析的首选报告项目)指南进行系统评价。美国国家医学图书馆(PubMed)的系统文献检索,WebofScience,Embase,进行了Scopus和Cochrane图书馆,其中涵盖了截至2022年7月发布的所有原创文章。条款,“TUDCA”与“视网膜”组合,“视网膜保护”,搜索了“神经保护”。使用采用的SYRCLE工具确定了可能的偏见。
结果:在423项最初收集的研究中,24篇文章符合全文审查的纳入/排除标准。其中六个是体外实验,17项研究报告了体内数据,一项研究描述了体外和体内数据。结果揭示了TUDCA对不同视网膜疾病的影响,如视网膜色素变性(RP),糖尿病视网膜病变(DR),视网膜变性(RD),视网膜神经节细胞(RGC)损伤,Leber的遗传性视神经病变(LHON),脉络膜新生血管(CNV),和视网膜脱离(RDT)。体内研究的质量评分为5至7分(共10分),根据SYRCLE的偏见工具的风险。体外和体内数据表明,TUDCA可以有效地延缓视网膜神经元的变性和凋亡,保留视网膜结构和功能,其作用机制可能与抑制细胞凋亡有关,减少炎症,减弱氧化应激,抑制内质网(ES)应激,减少血管生成。
结论:本系统综述表明TUDCA对视网膜疾病的体内和体外模型具有神经保护作用,加强现有证据表明TUDCA可能是视网膜疾病治疗中一种有前途的治疗剂。然而,精心设计的临床试验对于评估TUDCA在临床环境中的疗效是必要的。
BACKGROUND: Tauroursodeoxycholic acid (TUDCA) is a naturally produced hydrophilic bile acid that has been used for centuries in Chinese medicine. Numerous recent in vitro and in vivo studies have shown that TUDCA has neuroprotective action in various models of retinal disorders.
OBJECTIVE: To systematically
review the scientific literature and provide a comprehensive summary on the neuroprotective action and the mechanisms involved in the cytoprotective effects of TUDCA.
METHODS: A systematic
review was conducted in accordance with the PRISMA (The Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Systematic literature search of United States National Library of Medicine (PubMed), Web of Science, Embase, Scopus and Cochrane Library was performed, which covered all original articles published up to July 2022. The terms, \"TUDCA\" in combination with \"retina\", \"retinal protection\", \"neuroprotection\" were searched. Possible biases were identified with the adopted SYRCLE\'s tool.
RESULTS: Of the 423 initially gathered studies, 24 articles met inclusion/exclusion criteria for full-text
review. Six of them were in vitro experiments, 17 studies reported in vivo data and one study described both in vitro and in vivo data. The results revealed the effect of TUDCA on different retinal diseases, such as retinitis pigmentosa (RP), diabetic retinopathy (DR), retinal degeneration (RD), retinal ganglion cell (RGC) injury, Leber\'s hereditary optic neuropathy (LHON), choroidal neovascularization (CNV), and retinal detachment (RDT). The quality scores of the in vivo studies were ranged from 5 to 7 points (total 10 points), according to SYRCLE\'s risk of bias tool. Both in vitro and in vivo data suggested that TUDCA could effectively delay degeneration and apoptosis of retinal neurons, preserve retinal structure and function, and its mechanism of actions might be related with inhibiting apoptosis, decreasing inflammation, attenuating oxidative stress, suppressing endoplasmic reticulum (ER) stress, and reducing angiogenesis.
CONCLUSIONS: This systematic
review demonstrated that TUDCA has neuroprotective effect on in vivo and in vitro models of retinal disorders, reinforcing the currently available evidence that TUDCA could be a promising therapeutic agent in retinal diseases treatment. However, well designed clinical trials are necessary to appraise the efficacy of TUDCA in clinical setting.