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利用斑马鱼幼鱼研究肝脏疾病的方法。

Methods to Study Liver Disease Using Zebrafish Larvae.

机构信息

Program in Biology, New York University Abu Dhabi, Abu Dhabi, United Arab Emirates.

Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

出版信息

Methods Mol Biol. 2024;2707:43-69. doi: 10.1007/978-1-0716-3401-1_3.

DOI:10.1007/978-1-0716-3401-1_3
PMID:37668904
Abstract

Liver disease affects millions of people worldwide, and the high morbidity and mortality is attributed in part to the paucity of treatment options. In many cases, liver injury self-resolves due to the remarkable regenerative capacity of the liver, but in cases when regeneration cannot compensate for the injury, inflammation and fibrosis occur, creating a setting for the emergence of liver cancer. Whole animal models are crucial for deciphering the basic biological underpinnings of liver biology and pathology and, importantly, for developing and testing new treatments for liver disease before it progresses to a terminal state. The cellular components and functions of the zebrafish liver are highly similar to mammals, and zebrafish develop many diseases that are observed in humans, including toxicant-induced liver injury, fatty liver, fibrosis, and cancer. Therefore, the widespread use of zebrafish larvae for studying the mechanisms of these pathologies and for developing potential treatments necessitates the optimization of experimental approaches to assess liver disease in this model. Here, we describe protocols using staining methods, imaging, and gene expression analysis to assess liver injury, fibrosis, and preneoplastic changes in the liver of larval zebrafish.

摘要

肝脏疾病影响着全球数百万人,其高发病率和死亡率部分归因于治疗选择的匮乏。在许多情况下,由于肝脏具有出色的再生能力,肝损伤会自行恢复,但在再生无法代偿损伤的情况下,炎症和纤维化会发生,为肝癌的出现创造了条件。整体动物模型对于解析肝脏生物学和病理学的基本生物学基础至关重要,并且对于在疾病进展到终末期之前开发和测试治疗肝脏疾病的新方法也非常重要。斑马鱼肝脏的细胞成分和功能与哺乳动物高度相似,并且斑马鱼会患上许多在人类中观察到的疾病,包括毒物诱导的肝损伤、脂肪肝、纤维化和癌症。因此,广泛使用斑马鱼幼虫来研究这些疾病的发病机制并开发潜在的治疗方法,需要优化用于评估该模型中肝脏疾病的实验方法。在这里,我们描述了使用染色方法、成像和基因表达分析来评估斑马鱼幼虫肝脏损伤、纤维化和癌前病变的方案。

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Sustained effects of developmental exposure to inorganic arsenic on hepatic gsto2 expression and mating success in zebrafish.发育性暴露于无机砷对斑马鱼肝脏 gst02 表达和交配成功率的持续影响。

本文引用的文献

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Systematic Evaluation of the Effects of Toxicant Exposure on Survival in Zebrafish Embryos and Larvae.毒物暴露对斑马鱼胚胎和幼鱼生存影响的系统评价。
Curr Protoc. 2021 Sep;1(9):e231. doi: 10.1002/cpz1.231.
2
Single-Cell Transcriptomic Analysis Reveals a Hepatic Stellate Cell-Activation Roadmap and Myofibroblast Origin During Liver Fibrosis in Mice.单细胞转录组分析揭示了小鼠肝纤维化过程中肝星状细胞激活的轨迹和肌成纤维细胞的起源。
Hepatology. 2021 Nov;74(5):2774-2790. doi: 10.1002/hep.31987. Epub 2021 Aug 21.
3
Arsenic induced redox imbalance triggers the unfolded protein response in the liver of zebrafish.
Biol Open. 2024 Mar 1;13(3). doi: 10.1242/bio.060094. Epub 2024 Mar 6.
砷诱导的氧化还原失衡触发斑马鱼肝脏中的未折叠蛋白反应。
Toxicol Appl Pharmacol. 2020 Dec 15;409:115307. doi: 10.1016/j.taap.2020.115307. Epub 2020 Nov 2.
4
Observation and characterisation of macrophages in zebrafish liver.观察和分析斑马鱼肝脏中的巨噬细胞。
Micron. 2020 May;132:102851. doi: 10.1016/j.micron.2020.102851. Epub 2020 Feb 13.
5
Pediatric non-alcoholic fatty liver disease: current perspectives on diagnosis and management.小儿非酒精性脂肪性肝病:诊断与管理的当前观点
Pediatric Health Med Ther. 2019 Aug 23;10:89-97. doi: 10.2147/PHMT.S188989. eCollection 2019.
6
Transgenic strategies to generate heterogeneous hepatic cancer models in zebrafish.在斑马鱼中生成异质性肝癌模型的转基因策略。
J Mol Cell Biol. 2019 Dec 23;11(11):1021-1023. doi: 10.1093/jmcb/mjz083.
7
There Is Something Fishy About Liver Cancer: Zebrafish Models of Hepatocellular Carcinoma.肝癌的可疑之处:肝细胞癌的斑马鱼模型。
Cell Mol Gastroenterol Hepatol. 2019;8(3):347-363. doi: 10.1016/j.jcmgh.2019.05.002. Epub 2019 May 18.
8
Mannose Phosphate Isomerase and Mannose Regulate Hepatic Stellate Cell Activation and Fibrosis in Zebrafish and Humans.甘露糖磷酸异构酶和甘露糖调节斑马鱼和人类肝星状细胞的激活和纤维化。
Hepatology. 2019 Dec;70(6):2107-2122. doi: 10.1002/hep.30677. Epub 2019 May 24.
9
Rapid Analysis of Effects of Environmental Toxicants on Tumorigenesis and Inflammation Using a Transgenic Zebrafish Model for Liver Cancer.利用肝癌转基因斑马鱼模型快速分析环境毒物对肿瘤发生和炎症的影响。
Mar Biotechnol (NY). 2019 Jun;21(3):396-405. doi: 10.1007/s10126-019-09889-8. Epub 2019 Mar 9.
10
Transcriptomic profiles of tumor-associated neutrophils reveal prominent roles in enhancing angiogenesis in liver tumorigenesis in zebrafish.肿瘤相关中性粒细胞的转录组特征揭示了其在斑马鱼肝癌发生中促进血管生成的重要作用。
Sci Rep. 2019 Feb 6;9(1):1509. doi: 10.1038/s41598-018-36605-8.