Development of a convenient and rapid screening zebrafish model to investigate lethal effects and immunocompromised states of uremic toxins.

IF 3 3区医学 Q1 UROLOGY & NEPHROLOGY

Renal Failure Pub Date : 2025-12-01 Epub Date: 2025-06-08 DOI:10.1080/0886022X.2025.2514183

Pema Jo, Rui Zhang, Yuhua Zhang, Zhilian Li, Yanhua Wu, Shuqiong Zhang, Tsring Lhamo, Yuanhan Chen

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引用次数: 0

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusion: This zebrafish model provides a simple and rapid platform for studying the toxicological effects of uremic toxins and evaluating potential therapeutic interventions.

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建立一种方便、快速筛选的斑马鱼模型来研究尿毒症毒素的致死效应和免疫功能低下状态。

背景：尿毒症的特点是高死亡率和免疫功能障碍，由于尿毒症毒素的积累。传统的啮齿动物模型复杂且耗时。本研究旨在建立一种简单、快速的斑马鱼模型，用于研究尿毒症毒素的毒理学效应。方法：以腹膜透析废液为原料，采用透析法制备含有小毒血症毒素（SUT）和中毒血症毒素（MLUT）的尿毒症溶液。野生型斑马鱼幼鱼被用于评估死亡率，而转基因（TG）（zlyz:EGFP）斑马鱼，巨噬细胞被标记为绿色荧光蛋白，通过巨噬细胞迁移测定来评估免疫状态。结果：SUT治疗组和mlut治疗组的死亡率明显高于对照组，其中SUT的致死效果最强。在SUT和mlut治疗组中，巨噬细胞迁移明显受到抑制，表明免疫功能低下。该模型有效地模拟了尿毒症的致死性和免疫抑制作用。结论：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的治疗干预措施提供了一个简单、快速的平台。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Renal Failure 医学-泌尿学与肾脏学

CiteScore

3.90

自引率

13.30%

发文量

374

审稿时长

1 months

期刊介绍： Renal Failure primarily concentrates on acute renal injury and its consequence, but also addresses advances in the fields of chronic renal failure, hypertension, and renal transplantation. Bringing together both clinical and experimental aspects of renal failure, this publication presents timely, practical information on pathology and pathophysiology of acute renal failure; nephrotoxicity of drugs and other substances; prevention, treatment, and therapy of renal failure; renal failure in association with transplantation, hypertension, and diabetes mellitus.