Department of Toxicology, School of Public Health, Jilin University, Changchun, 130021, Jilin, People's Republic of China,
Cardiovasc Toxicol. 2013 Sep;13(3):194-207. doi: 10.1007/s12012-013-9198-y.
The purpose of this work was to investigate the cardiovascular toxicity of different sizes and different dosages of silica nanoparticles in Wistar rats. The three silica nanoparticles (30, 60, and 90 nm) and one fine silica particles (600 nm) at three doses of 2, 5, and 10 (mg/Kg bw) were used in the present experiment. After intratracheal instillation for a total of 16 times, concentration of Si in hearts and serum was measured by inductively coupled plasma optical emission spectrometer. The hematology parameters were analyzed by an automated hematology analyzer, and the inflammatory reaction, oxidative stress, endothelial dysfunction, and the myocardial enzymes in serum were measured by kits. Our results showed intratracheal-instilled silica nanoparticles could pass through the alveolar-capillary barrier into systemic circulation. Concentration of Si in the heart and serum depended on the particles size and dosage. The levels of reactive oxygen species (ROS) at 5, 10 mg/Kg bw of the three silica nanoparticles were higher than the fine silica particles. Blood levels of inflammation-related high-sensitivity C-reactive protein and cytokines such as interleukin-1beta (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-alpha were increased after exposure to three silica nanoparticles at 10 mg/Kg bw. Moreover, the levels of IL-1β and IL-6 at 10 mg/Kg bw of silica nanoparticles (30 nm) were higher than the fine silica particles. Significant decrease in superoxide dismutase, glutathione peroxidase and significant increase in malondialdehyde were observed at 10 mg/Kg bw of the three silica nanoparticles. A significant decrease in nitric oxide (NO) production was induced which coincided with the reduction of nitric oxide synthase (NOS) activity and the excessive generation of ROS in rats. The levels of intercellular adhesion molecule-l and vascular cell adhesion molecule-l elevated significantly after exposure to three silica nanoparticles at 10 mg/Kg bw, which are considered as early steps of endothelial dysfunction. We conclude that cardiovascular toxicity of silica nanoparticles could be related to the particles size and dosage. Oxidative stress could be involved in inflammatory reaction and endothelial dysfunction, all of which could aggravate cardiovascular toxicology. In addition, endothelial NO/NOS system disorder caused by nanoparticles could be one of the mechanisms for endothelial dysfunction.
本研究旨在探讨不同粒径和不同剂量的二氧化硅纳米颗粒对 Wistar 大鼠心血管系统的毒性作用。实验采用三种不同粒径的二氧化硅纳米颗粒（30nm、60nm 和 90nm）和一种细颗粒二氧化硅（600nm），分别设 2、5 和 10mg/kg 三个剂量，通过气管滴注共 16 次。采用电感耦合等离子体原子发射光谱仪（ICP-OES）测定心脏和血清中的硅浓度，全自动血液分析仪分析血液学参数，试剂盒检测血清中的炎症反应、氧化应激、内皮功能障碍和心肌酶。结果显示，气管滴注二氧化硅纳米颗粒可穿过肺泡毛细血管屏障进入体循环，心脏和血清中的硅浓度与颗粒粒径和剂量有关。5、10mg/kg 三种二氧化硅纳米颗粒的活性氧（ROS）水平均高于细颗粒二氧化硅。10mg/kg 三种二氧化硅纳米颗粒可使炎症相关的高敏 C 反应蛋白和白细胞介素-1β（IL-1β）、白细胞介素-6（IL-6）、肿瘤坏死因子-α（TNF-α）等细胞因子水平升高，10mg/kg 二氧化硅纳米颗粒（30nm）可使 IL-1β 和 IL-6 水平高于细颗粒二氧化硅。三种二氧化硅纳米颗粒在 10mg/kg 剂量下可使超氧化物歧化酶、谷胱甘肽过氧化物酶活性降低，丙二醛水平升高。一氧化氮（NO）生成减少，一氧化氮合酶（NOS）活性降低，ROS 生成过多。10mg/kg 三种二氧化硅纳米颗粒可使细胞间黏附分子-1 和血管细胞黏附分子-1 水平升高，提示内皮功能障碍早期。综上，二氧化硅纳米颗粒的心血管毒性与颗粒粒径和剂量有关，氧化应激可能参与炎症反应和内皮功能障碍，从而加重心血管毒性。此外，纳米颗粒引起的内皮一氧化氮/一氧化氮合酶系统紊乱可能是内皮功能障碍的机制之一。
