中关村旭月非损伤微测技术产业联盟 - Part Fibre Toxicol : 钙流为纳米硅通过钙-ROS诱导器官损伤提供关键证据

Part Fibre Toxicol : 钙流为纳米硅通过钙-ROS诱导器官损伤提供关键证据 | NMT材料毒理创新科研平台

NMT作为生命科学底层核心技术，是建立活体创新科研平台的必备技术。2005年~2020年，NMT已扎根中国15年。2020年，中国NMT销往瑞士苏黎世大学，正式打开欧洲市场。

研究使用平台：NMT材料毒理创新科研平台
期刊：Particle and Fibre Toxicology
主题：NMT钙流为纳米硅通过Ca2+-ROS诱导器官损伤提供关键证据
标题：Silica nanomaterials induce organ injuries by Ca2+-ROS-initiated disruption of the endothelial barrier and triggering intravascular coagulation
影响因子：6.561
检测指标：Ca2+流速
检测样品：脐带静脉内皮细胞
Ca²⁺流实验处理方法：
内皮细胞100μg/mL的SiNPs瞬时处理
Ca²⁺流实验测试液成份：
120mM NaCl，3mM KCl，2.5mM CaCl₂,1mM MgCl₂,1.25mM NaH₂PO₄，25mM NaHCO₃，10mM 葡萄糖
作者：山西医科大学曹济民、王昭君

样品检测视频：藻细胞检测

中文摘要（谷歌机翻）

二氧化硅纳米颗粒（SiNPs）在许多领域的日益广泛使用引起了人们对毒性的关注。我们研究了SiNP-20（粒径20 nm）和SiNP-100（100 nm）的毒性及其潜在机制，重点是在体内外的内皮细胞。本研究使用多种技术在培养的人脐静脉内皮细胞（HUVEC）和成年雌性Balb / c小鼠中进行。

在体外，SiNP-20和SiNP-100均降低了培养的HUVEC的活力并损坏了其质膜。纳米颗粒还以浓度依赖的方式抑制HUVEC的迁移和管的形成。两种SiNP均诱导显着的钙动员和活性氧（ROS）的产生，增加了酪氨酸731残基（pY731-VEC）处血管内皮（VE）钙粘蛋白的磷酸化，降低了VE-钙粘蛋白的表达，破坏了HUVECs中的连接性VE钙黏着蛋白连续性和诱导的F-肌动蛋白重组。通过用YM58483阻断Ca2+释放激活的Ca2+（CRAC）通道或通过用N-乙酰基半胱氨酸（NAC）消除ROS来扭转损伤。

在体内，SiNP-20和SiNP-100（iv）均可引起Balb / c小鼠多器官损伤，其剂量（范围为7–35 mg / kg），粒径和暴露时间（4–72 h）取决于方式。心脏损伤包括冠状动脉内皮损伤，红细胞粘附于冠状动脉内膜和冠状动脉凝血。腹主动脉损伤表现出内膜肿瘤形成。肺损伤为较小的肺静脉凝血，细支气管上皮水肿和管腔渗血和变窄。肝损伤包括多灶性坏死和较小的肝静脉充血和凝血。肾损伤涉及肾小球充血和肿胀。

SiNPs暴露后，所有观察到的器官组织均发生巨噬细胞浸润。SiNP还降低了体内多个器官组织中VE-钙粘蛋白的表达并改变了VE钙粘蛋白的空间分布。最大的SiNP（SiNP-100）和最长的暴露时间在体内和体外均表现出最大的毒性。

d, results of non-invasive micro-test (NMT) showing abrupt induction of Ca2+ influx by either SiNP-20 or SiNP-100 (100 μg/mL) in HUVECs. Downward currents represented Ca2+ influx while upward currents represented Ca2+ efflux in this method. e, statistical results of NMT indicating the average Ca2+Ca2+ influx induced by SiNP-20 and SiNP-100. SiNP-100 induced more Ca2+ influx than SiNP-20 (*** p < 0.001), n = 4 cells for each treatment

联盟推荐抗疫产品之一：新冠肺炎中医治疗NMT创新平台
点击查看产品详情

英文摘要

The growing use of silica nanoparticles (SiNPs) in many fields raises human toxicity concerns. We studied the toxicity of SiNP-20 (particle diameter 20 nm) and SiNP-100 (100 nm) and the underlying mechanisms with a focus on the endothelium both in vitro and in vivo.The study was conducted in cultured human umbilical vein endothelial cells (HUVECs) and adult female Balb/c mice using several techniques.

In vitro, both SiNP-20 and SiNP-100 decreased the viability and damaged the plasma membrane of cultured HUVECs. The nanoparticles also inhibited HUVECs migration and tube formation in a concentrationdependent manner. Both SiNPs induced significant calcium mobilization and generation of reactive oxygen species (ROS), increased the phosphorylation of vascular endothelial (VE) cadherin at the site of tyrosine 731 residue (pY731- VEC), decreased the expression of VE-cadherin expression, disrupted the junctional VE cadherin continuity and induced F-actin re-assembly in HUVECs. The injuries were reversed by blocking Ca2+ release activated Ca2+ (CRAC) channels with YM58483 or by eliminating ROS with N-acetyl cysteine (NAC).

In vivo, both SiNP-20 and SiNP-100 (i.v.) induced multiple organ injuries of Balb/c mice in a dose (range 7–35 mg/kg), particle size, and exposure time (4–72 h)-dependent manner. Heart injuries included coronary endothelial damage, erythrocyte adhesion to coronary intima and coronary coagulation. Abdominal aorta injury exhibited intimal neoplasm formation. Lung injuries were smaller pulmonary vein coagulation, bronchiolar epithelial edema and lumen oozing and narrowing. Liver injuries included multifocal necrosis and smaller hepatic vein congestion and coagulation. Kidney injuries involved glomerular congestion and swelling.

Macrophage infiltration occurred in all of the observed organ tissues after SiNPs exposure. SiNPs also decreased VE-cadherin expression and altered VE cadherin spatial distribution in multiple organ tissues in vivo. The largest SiNP (SiNP-100) and longest exposure time exerted the greatest toxicity both in vitro and in vivo.

中关村NMT联盟“一带一路”全国测试服务网络测试服务信息

Part Fibre Toxicol : 钙流为纳米硅通过钙-ROS诱导器官损伤提供关键证据 | NMT材料毒理创新科研平台