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斑马鱼作为心血管和代谢疾病的模型:精准医学的未来。

Zebrafish as a Model for Cardiovascular and Metabolic Disease: The Future of Precision Medicine.

作者信息

Angom Ramcharan Singh, Nakka Naga Malleswara Rao

机构信息

Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine and Science, 4500 San Pablo Road South, Jacksonville, FL 32224, USA.

出版信息

Biomedicines. 2024 Mar 20;12(3):693. doi: 10.3390/biomedicines12030693.

Abstract

The zebrafish () has emerged as an appreciated and versatile model organism for studying cardiovascular and metabolic diseases, offering unique advantages for both basic research and drug discovery. The genetic conservation between zebrafish and humans and their high fecundity and transparent embryos allow for efficient large-scale genetic and drug-oriented screening studies. Zebrafish possess a simplified cardiovascular system that shares similarities with mammals, making them particularly suitable for modeling various aspects of heart development, function, and disease. The transparency of zebrafish embryos enables the real-time visualization of cardiovascular dynamics, offering insights into early embryonic events and facilitating the study of heart-related anomalies. In metabolic research, zebrafish provide a cost-effective platform for modeling obesity, type 2 diabetes, hyperlipidemia, and other metabolic disorders. Their high reproductive rate allows for the generation of large cohorts for robust statistical analyses, while advanced genetic tools, such as CRISPR/Cas9, enable precise gene editing with which to model specific genetic mutations associated with human diseases. Zebrafish metabolic models have been instrumental in elucidating the molecular mechanisms underlying metabolic diseases, studying the effects of environmental factors, and identifying potential therapeutic targets. Additionally, the permeability of zebrafish embryos to small molecules facilitates drug discovery and screening, offering a rapid and economical approach to identifying compounds with therapeutic potential. In conclusion, zebrafish cardiovascular and metabolic disease models continue to contribute significantly to our perception of disease pathogenesis, providing a platform for translational research and developing novel therapeutic interventions. The versatility, scalability, and genetic manipulability of zebrafish position them as an invaluable asset in unraveling the complexities of cardiovascular and metabolic diseases. This review presents an overview of the zebrafish model's key features and contributions to investigating cardiovascular and metabolic disorders. We discuss the benefits and drawbacks of using zebrafish models to study human disease and the critical findings revealed by the progress in this endeavor to date.

摘要

斑马鱼已成为研究心血管和代谢疾病的一种备受青睐且用途广泛的模式生物,在基础研究和药物发现方面都具有独特优势。斑马鱼与人类之间的基因保守性以及它们的高繁殖力和透明胚胎,使得大规模高效的基因和药物导向筛选研究成为可能。斑马鱼拥有一个与哺乳动物相似的简化心血管系统,这使其特别适合对心脏发育、功能和疾病的各个方面进行建模。斑马鱼胚胎的透明性能够实时观察心血管动态,有助于深入了解早期胚胎事件,并促进对心脏相关异常的研究。在代谢研究中,斑马鱼为肥胖、2型糖尿病、高脂血症和其他代谢紊乱的建模提供了一个经济高效的平台。它们的高繁殖率使得能够产生大量用于可靠统计分析的群体,而先进的基因工具,如CRISPR/Cas9,能够进行精确的基因编辑,从而对与人类疾病相关的特定基因突变进行建模。斑马鱼代谢模型在阐明代谢疾病的分子机制、研究环境因素的影响以及确定潜在治疗靶点方面发挥了重要作用。此外,斑马鱼胚胎对小分子的渗透性有助于药物发现和筛选,为识别具有治疗潜力的化合物提供了一种快速且经济的方法。总之,斑马鱼心血管和代谢疾病模型继续为我们对疾病发病机制的认识做出重大贡献,为转化研究和开发新型治疗干预措施提供了一个平台。斑马鱼的多功能性、可扩展性和基因可操作性使其成为揭示心血管和代谢疾病复杂性的宝贵资产。本综述概述了斑马鱼模型在研究心血管和代谢紊乱方面的关键特征和贡献。我们讨论了使用斑马鱼模型研究人类疾病的利弊以及迄今为止这一努力所揭示的关键发现。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/80c9/10968160/28b4108f9e8f/biomedicines-12-00693-g001.jpg

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