斑马鱼在炎症性肠病机制及药物研究中的应用进展

doi:10.12300/j.issn.1674-5817.2024.170

实验动物与比较医学 ›› 2025, Vol. 45 ›› Issue (4): 422-431.DOI: 10.12300/j.issn.1674-5817.2024.170

斑马鱼在炎症性肠病机制及药物研究中的应用进展

赵鑫, 王晨曦, 石文清, 娄月芬()()

同济大学附属上海市第四人民医院药剂科, 上海 200434

收稿日期:2024-11-13 修回日期:2025-02-04 出版日期:2025-08-25 发布日期:2025-09-01
通讯作者:
娄月芬（1974—），女，硕士，主任药师，研究方向：药事管理与临床药学研究。E-mail： louyuefen@tongji.edu.cn。ORCID：0009-0005-9622-6059
作者简介:赵鑫（1986—），女，博士，主管药师，研究方向：药效物质基础与临床药学研究。E-mail： zhaoxin1@tongji.edu.cn
基金资助:
上海市第四人民医院科研启动项目“基于肠道菌群-炎症反应探讨‘黄芩-黄连’药对‘相须’干预溃疡性结肠炎的作用机制和药效物质研究”(sykyqd09601)

Advances in the Application of Zebrafish in the Research of Inflammatory Bowel Disease Mechanisms and Drug Development

ZHAO Xin, WANG Chenxi, SHI Wenqing, LOU Yuefen()()

Department of Pharmacy, Shanghai Fourth People's Hospital, School of Medicine, Tongji University, Shanghai 200434, China

Received:2024-11-13 Revised:2025-02-04 Published:2025-08-25 Online:2025-09-01
Contact: LOU Yuefen (ORCID: 0009-0005-9622-6059), E-mail: louyuefen@tongji.edu.cn

摘要/Abstract

摘要：

炎症性肠病（inflammatory bowel disease，IBD）是一类由遗传、免疫、环境等多因素共同驱动的慢性复发性肠道疾病，主要包括溃疡性结肠炎（ulcerative colitis）和克罗恩病（Crohn's disease）2种类型。当前的IBD疾病研究中，小鼠与斑马鱼是最常用的实验动物。其中，斑马鱼凭借其独特优势成为理想模型。相较于啮齿类动物，斑马鱼具有生长周期短、繁殖能力强、体型小巧及胚胎透明等特点，不仅便于动态追踪连续性病理变化，还能高效实现高通量药物筛选。斑马鱼的基因与人类同源性达70%以上，肠道细胞组成及发育过程与人类高度相似，且其肠道菌群与人类肠道微生态特征接近，为研究肠道菌群与IBD的关联奠定了良好基础。随着生物技术的发展，基于化学诱导和基因工程构建的斑马鱼IBD模型，可精准模拟人类IBD的核心病理特征，如肠壁增厚、炎性细胞浸润、促炎因子表达升高等，该模型在揭示发病机制和开发靶向药物中发挥了关键作用。本文首先阐述斑马鱼的肠道特征及IBD模型特点，进而从遗传、免疫、环境与饮食、感染等维度深入剖析其在IBD发病机制研究中的应用，同时综述其在抗炎药物、益生菌、中药等治疗药物开发中的研究进展，旨在为科研工作者在临床前研究的各阶段合理运用斑马鱼模型提供参考，以推动IBD基础研究领域的深入发展，并期望能加速该领域的突破。

关键词: 斑马鱼, 炎症性肠病, 药物研究, 动物模型

Abstract:

Inflammatory bowel disease (IBD) is a chronic, relapsing intestinal disorder driven by multiple factors including genetics, immunity, and environment, and is clinically classified into ulcerative colitis and Crohn's disease. Currently, mice and zebrafish are the primary experimental animals used in IBD research, among which zebrafish have emerged as an ideal model due to their unique advantages. Compared with rodent models, zebrafish serve as an effective and convenient model, offering advantages such as a short life cycle, robust reproductive capacity, small size, and transparent embryos. These characteristics make zebrafish highly suitable for dynamic tracking of continuous pathological progression and high-throughput drug screening. Zebrafish share over 70% genetic homology with humans, and their intestinal cellular composition and ontogeny closely resemble those of humans. Moreover, the structure and characteristics of their gut microbiota are similar to the human intestinal microbiome, providing a solid foundation for studying the relationship between gut microbiota and IBD. With advances in biotechnology, zebrafish IBD models generated by chemical induction or genetic engineering can accurately simulate the core pathological features of human IBD, such as intestinal wall thickening, inflammatory cell infiltration, and elevated expression of pro-inflammatory factors. These models have played a significant role in revealing the pathogenesis of IBD as well as the development of targeted therapeutic drugs. This article first outlines the intestinal characteristics of zebrafish and features of zebrafish IBD models, then provides an in-depth analysis of their application in IBD pathogenesis research from multiple aspects, including genetics, immunity, environment and diet, and infection. It also reviews research progress on the application of zebrafish in the development of anti-inflammatory drugs, probiotics, and traditional Chinese medicine therapies, aiming to provide researchers with references for the rational use of zebrafish models at all stages of preclinical research, to advance fundamental IBD research and accelerate breakthroughs in this field.

Key words: Zebrafish, Inflammatory bowel disease, Drug research, Animal model

中图分类号:

Q95-33

赵鑫,王晨曦,石文清,等. 斑马鱼在炎症性肠病机制及药物研究中的应用进展[J]. 实验动物与比较医学, 2025, 45(4): 422-431. DOI: 10.12300/j.issn.1674-5817.2024.170.

ZHAO Xin,WANG Chenxi,SHI Wenqing,et al. Advances in the Application of Zebrafish in the Research of Inflammatory Bowel Disease Mechanisms and Drug Development[J]. Laboratory Animal and Comparative Medicine, 2025, 45(4): 422-431. DOI: 10.12300/j.issn.1674-5817.2024.170.

图/表 1

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斑马鱼在炎症性肠病机制及药物研究中的应用进展

Advances in the Application of Zebrafish in the Research of Inflammatory Bowel Disease Mechanisms and Drug Development

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