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鲍奕清.伊马替尼在斑马鱼血管和神经发育过程中的作用研究[J].中国实验动物学报,2020,28(3):289~296.
伊马替尼在斑马鱼血管和神经发育过程中的作用研究
Study on the effects of imatinib on the development of blood vessels and nerves in zebrafish
投稿时间:2019-12-24  
DOI:10. 3969 / j.issn.1005-4847. 2020. 03. 001
中文关键词:  伊马替尼  血管新生  内皮细胞  神经元  斑马鱼
英文关键词:imatinib  angiogenesis  endothelial cell  neuron  zebrafish
基金项目:
作者单位E-mail
鲍奕清 南通大学神经再生重点实验室,生命科学学院,医学院,江苏 南通 226001 344789853@ qq.com 
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中文摘要:
      目的 利用斑马鱼胚胎透明便于活体成像的优势,研究伊马替尼在斑马鱼血管和神经发育过程中的作用。 方法 首先利用野生型斑马鱼胚胎检测伊马替尼对血管和神经早期发育阶段斑马鱼胚胎的安全浓度范围。在此浓度范围内对标记血管系统的转基因斑马鱼胚胎进行伊马替尼处理,并对血管和神经细胞共标的斑马鱼进行伊马替尼处理研究其对血管新生抑制的同时对神经元的影响。初步探讨伊马替尼抑制血管新生的分子机制。 结果 伊马替尼浓度低于 100 μg / mL 对斑马鱼胚胎发育无致死作用。在此浓度范围,伊马替尼显著抑制斑马鱼节 间血管(intersegmental vessel,ISV)的发育,包括 ISV 的腔化过程及内皮细胞的增殖。此外,伊马替尼对斑马鱼运动神经元及神经元前体细胞的发育过程无显著影响。并且,基因表达分析显示伊马替尼能够显著抑制 vegfr2pdgfrα mRNA 表达。 结论 伊马替尼通过调控 VEGF 和 PDGFR 信号途径抑制斑马鱼血管新生。
英文摘要:
      Objective Using the advantages of zebrafish embryo transparency for live imaging, the role of imatinib in the development of blood vessels and nerves in zebrafish was studied. Methods First, we investigated the safe concentration range of imatinib for zebrafish in the blood vessel and neuron development stage using wild type zebrafish embryos. Within the safe concentration range, transgenic zebrafish embryos with a labeled vascular system were treated with imatinib. Moreover, endothelial cell and neuron co-labeled zebrafish were treated with imatinib to study the specificity for angiogenesis inhibition. The molecular mechanism of imatinib-inhibited angiogenesis was investigated. Results Imatinib concentration below 100 μg / mL was not lethal to zebrafish embryos. In this concentration, imatinib significantly inhibited the development of zebrafish intersegmental vessels (ISVs), including the process of ISV lumenization and the proliferation of endothelial cells. Additionally, imatinib had no significant effect on motor neurons and neuronal precursor cells. Moreover, gene expression analysis showed that imatinib was able to significantly inhibit vegfr2 and pdgfrα mRNA expression. Conclusions Imatinib significantly inhibited angiogenesis in zebrafish embryos by regulating VEGF and PDGFR signals.
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