Chang Jie, Ichihara Gaku, Shimada Yasuhito, Tada-Oikawa Saeko, Kuroyanagi Junya, Zhang Beibei, Suzuki Yuka, Sehsah Radwa, Kato Masashi, Tanaka Toshio, Ichihara Sahoko
J Nanosci Nanotechnol. 2015 Mar;15(3):2140-7. doi: 10.1166/jnn.2015.9762.
The present study investigated the effects of exposure to metal oxide nanoparticles on vasculogenesis/angiogenesis using transgenic zebrafish. The study also examined the potential mechanisms involved in those effects using human umbilical vein endothelial cells (HUVEC). TG (nacre/fli1:EGFP) zebrafish were exposed to nano-sized titanium dioxide (TiO2), silica dioxide (SiO2), and copper oxide (CuO) particles at 0.01, 1 and 100 µg/ml concentrations from 1 to 5 dpf (day-post-fertilization). Angiogenesis was evaluated morphologically at the end of exposure. Exposure to CuO nanoparticles reduced the number of transversely-running subintestinal vessels in TG zebrafish. Exposure to CuO nanoparticles down-regulated the expression of vascular endothelial growth factor (VEGF) and VEGF receptor in endothelial cells sorted by Fluorescence Activated Cell Sorter (FACS). Exposure of HUVEC to CuO nanoparticles reduced cell viability and increased apoptotic index in a dose-dependent manner. The results suggested that CuO nanoparticles inhibit vasculogenesis through reduction of VEGF expression and induction of apoptosis.
本研究使用转基因斑马鱼调查了暴露于金属氧化物纳米颗粒对血管生成/血管新生的影响。该研究还使用人脐静脉内皮细胞（HUVEC）检查了这些影响所涉及的潜在机制。将TG（珍珠母/fli1:EGFP）斑马鱼在受精后1至5天（dpf）暴露于浓度为0.01、1和100μg/ml的纳米级二氧化钛（TiO2）、二氧化硅（SiO2）和氧化铜（CuO）颗粒。在暴露结束时从形态学上评估血管新生。暴露于CuO纳米颗粒会减少TG斑马鱼中横向运行的肠下血管数量。通过荧光激活细胞分选仪（FACS）分选的内皮细胞中，暴露于CuO纳米颗粒会下调血管内皮生长因子（VEGF）和VEGF受体的表达。HUVEC暴露于CuO纳米颗粒会以剂量依赖的方式降低细胞活力并增加凋亡指数。结果表明，CuO纳米颗粒通过降低VEGF表达和诱导凋亡来抑制血管生成。
