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100μg/m L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vegfr2和pdgfrαmRNA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。
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 100μg/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 pdgfrαmRNA expression.Conclusions Imatinib significantly inhibited angiogenesis in zebrafish embryos by regulating VEGF and PDGFR signals.
作者
鲍奕清
陈思
洪瑞晟
朱仪
高敏
李乐乐
张旭
王新
刘东
石运伟
BAO Yiqing;CHEN Si;HONG Ruisheng;ZHU Yi;GAO Min;LI Lele;ZHANG Xu;WANG Xin;LIU Dong;SHI Yunwei(Key Laboratory of Neuroregeneration,School of Life Science,Medical School,Nantong University,Nantong 226001,China)
出处
《中国实验动物学报》
CAS
CSCD
北大核心
2020年第3期289-296,共8页
Acta Laboratorium Animalis Scientia Sinica
基金
国家自然科学基金面上项目(81970432)
江苏省大学生创新创业训练计划(201810304030Z)。
