Silica nanoparticles inhibit macrophage activity and angiogenesis via VEGFR2-mediated MAPK signaling pathway in zebrafish embryos
Silica nanoparticles inhibit macrophage activity and angiogenesis via VEGFR2-mediated MAPK signaling pathway in zebrafish embryos
复制标题
二氧化硅纳米颗粒通过 VEGFR2 介导的 MAPK 信号通路抑制斑马鱼胚胎中的巨噬细胞活性和血管生成
DOI：
10.1016/j.chemosphere.2017.05.138
复制
发表时间：
2017-09-01
期刊：
影响因子：
8.8
通讯作者：
Sun, Zhiwei
中科院分区：
文献类型：
--
作者：
Duan, Junchao;Hu, Hejing;Sun, Zhiwei
由于二氧化硅纳米粒子在食品、化工、生物医学等领域的广泛应用，其安全性评价受到广泛关注。然而，SiNPs对心血管系统，尤其是对血管生成的不良影响及其机制尚不清楚。本研究旨在阐明SiNPs对转基因斑马鱼Tg（fli-1：EGFP）和白化病血管生成的可能机制。SiNPs通过静脉内微量注射以剂量依赖的方式引起心血管畸形。心血管畸形的发生率依次为心包水肿>心动过缓>血虚。SiNPs处理组斑马鱼胚胎肠下血管（subintestinal vessels，SIV）面积显著减少，血管内皮细胞表达减弱。中性红染色显示，巨噬细胞数量减少，而巨噬细胞抑制率呈剂量依赖性升高。SiNPs还能显著降低巨噬细胞活性相关基因巨噬细胞移动抑制因子（MIF）和血管生成相关基因血管内皮生长因子受体2（VEGFR 2）的mRNA表达。SiNPs处理后，斑马鱼p-Erk 1/2和p-p38 MAPK蛋白水平显著降低。我们的研究结果表明SiNPs通过下调MAPK信号通路抑制巨噬细胞活性和血管生成。(C)2017爱思唯尔有限公司版权所有
The safety evaluation of silica nanoparticles (SiNPs) are getting great attention due to its widely-used in food sciences, chemical industry and biomedicine. However, the adverse effect and underlying mechanisms of SiNPs on cardiovascular system, especially on angiogenesis is still unclear. This study was aimed to illuminate the possible mechanisms of SiNPs on angiogenesis in zebrafish transgenic lines, Tg(fli-1:EGFP) and Albino. SiNPs caused the cardiovascular malformations in a dose-dependent manner via intravenous microinjection. The incidences of cardiovascular malformations were observed as: Pericardial edema > Bradycardia > Blood deficiency. The area of subintestinal vessels (SIVs) was significant reduced in SiNPs-treated groups, accompanied with the weaken expression of vascular endothelial cells in zebrafish embryos. Using neutral red staining, the quantitative number of macrophage was declined; whereas macrophage inhibition rate was elevated in a dose-dependent way. Furthermore, SiNPs significantly decreased the mRNA expression of macrophage activity related gene, macrophage migration inhibitory factor (MIF) and the angiogenesis related gene, vascular endothelial growth factor receptor 2 (VEGFR2). The protein levels of p-Erkl /2 and p-p38 MAPK were markedly decreased in zebrafish exposed to SiNPs. Our results implicate that SiNPs inhibited the macrophage activity and angiogenesis via the downregulation of MAPK singaling pathway. (C) 2017 Elsevier Ltd. All rights reserved.