Fujii Kensuke, Yamakawa Kazuma, Takeda Yuriko, Okuda Natsuko, Takasu Akira, Ono Fumihito
Department of Emergency and Critical Care Medicine, Osaka Medical and Pharmaceutical University, 2-7 Daigakumachi, Takatsuki, Osaka, 569-8686, Japan.
Department of Physiology, Osaka Medical and Pharmaceutical University, 2-7 Daigakumachi, Takatsuki, Osaka, 569-8686, Japan.
Intensive Care Med Exp. 2024 Jan 31;12(1):8. doi: 10.1186/s40635-024-00595-x.
The models used to investigate the pathophysiological mechanisms of acute critical illness are not limited to mammalian species. The zebrafish (Danio rerio) is a popular model organism for studying diseases due to its transparency and rapid development. The genes and signaling pathways involved in acute critical illness appear highly conserved among zebrafish and humans. Forward genetics such as random mutagenesis by a chemical mutagen or reverse genetics methods represented by CRISPR/Cas9 allowed researchers to reveal multiple novel aspects of pathological processes in areas including infection, immunity, and regeneration. As a model of sepsis, transgenic zebrafish allowed the visualization of lipopolysaccharide (LPS)-induced vascular leakage in vivo and the demonstration of changes in the expression of cellular junction proteins. Other transgenic zebrafish visualizing the extravascular migration of neutrophils and macrophages have demonstrated a decrease in neutrophil numbers and an increased expression of an inflammatory gene, which replicates a phenomenon observed in humans in clinically encountered sepsis. The regenerative potential and the visibility of zebrafish organs also enabled clarification of important mechanisms in wound healing, angiogenesis, and neurogenesis. After spinal cord injury (SCI), a marker gene expressed in glial bridging was discovered. Furthermore, localized epithelial-to-mesenchymal transition (EMT) and molecular mechanisms leading to spinal cord repair were revealed. These translational studies using zebrafish show the potential of the model system for the treatment of acute critical illnesses such as sepsis, organ failure, and trauma.
用于研究急性危重病病理生理机制的模型并不局限于哺乳动物物种。斑马鱼（Danio rerio）因其透明性和快速发育，是一种用于研究疾病的常用模式生物。斑马鱼和人类之间，参与急性危重病的基因和信号通路似乎高度保守。正向遗传学方法，如化学诱变剂诱导的随机诱变，以及以CRISPR/Cas9为代表的反向遗传学方法，使研究人员能够揭示感染、免疫和再生等领域病理过程的多个新方面。作为脓毒症模型，转基因斑马鱼能够在体内可视化脂多糖（LPS）诱导的血管渗漏，并证明细胞连接蛋白表达的变化。其他可视化中性粒细胞和巨噬细胞血管外迁移的转基因斑马鱼，已证明中性粒细胞数量减少和炎症基因表达增加，这重现了临床上脓毒症患者中观察到的现象。斑马鱼的再生潜力和器官的可视性，也有助于阐明伤口愈合、血管生成和神经发生中的重要机制。脊髓损伤（SCI）后，发现了一种在胶质桥中表达的标记基因。此外，还揭示了局部上皮-间充质转化（EMT）和导致脊髓修复的分子机制。这些使用斑马鱼的转化研究表明，该模型系统在治疗脓毒症、器官衰竭和创伤等急性危重病方面具有潜力。
