Jo Pema, Zhang Rui, Zhang Yuhua, Li Zhilian, Wu Yanhua, Zhang Shuqiong, Lhamo Tsring, Chen Yuanhan
Department of Internal Medicine, Second Ward, Nyingchi People's Hospital, Nyingchi, China.
Division of Nephrology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China.
Ren Fail. 2025 Dec;47(1):2514183. doi: 10.1080/0886022X.2025.2514183. Epub 2025 Jun 8.
Uremia is characterized by high mortality and immune dysfunction owing to the accumulation of uremic toxins. Traditional rodent models are complex and time consuming. This study aimed to develop a simple and rapid zebrafish model for investigating the toxicological effects of uremic toxins.
Uremic solutions containing small (SUT) and medium-to-large (MLUT) uremic toxins were prepared using waste solution of peritoneal dialysis by a dialysis method. Wild-type zebrafish larvae were used to assess mortality, whereas transgenic (TG) (zlyz:EGFP) zebrafish, with macrophages labeled with green fluorescent protein, were used to evaluate immune status through macrophage migration assays.
The mortality rates were significantly higher in the SUT- and MLUT-treated groups than in the controls, with SUT showing the strongest lethal effect. Macrophage migration was significantly inhibited in both SUT- and MLUT-treated groups, indicating an immunocompromise. This model effectively mimicked the lethal and immunosuppressive effects of uremia.
This zebrafish model provides a simple and rapid platform for studying the toxicological effects of uremic toxins and evaluating potential therapeutic interventions.
尿毒症的特征是由于尿毒症毒素的积累导致高死亡率和免疫功能障碍。传统的啮齿动物模型复杂且耗时。本研究旨在开发一种简单快速的斑马鱼模型，用于研究尿毒症毒素的毒理学效应。
通过透析法使用腹膜透析废液制备含有小分子（SUT）和中大分子（MLUT）尿毒症毒素的尿毒症溶液。野生型斑马鱼幼虫用于评估死亡率，而巨噬细胞用绿色荧光蛋白标记的转基因（TG）（zlyz:EGFP）斑马鱼则通过巨噬细胞迁移试验来评估免疫状态。
SUT组和MLUT组的死亡率显著高于对照组，其中SUT的致死作用最强。SUT组和MLUT组的巨噬细胞迁移均受到显著抑制，表明存在免疫功能受损。该模型有效模拟了尿毒症的致死和免疫抑制作用。
该斑马鱼模型为研究尿毒症毒素的毒理学效应和评估潜在治疗干预措施提供了一个简单快速的平台。
