Department of General Medicine, General Hospital of Ningxia Medical University, Yinchuan, Ningxia, People's Republic of China.
Department of Pharmaceutical Sciences, Biomanufacturing Research Institute and Technological Enterprise (BRITE), North Carolina Central University, Durham, NC, USA.
Int J Nanomedicine. 2020 Jan 30;15:633-645. doi: 10.2147/IJN.S232986. eCollection 2020.
With the increased application of Silver nanoparticles (AgNP), its potential concerns to the health of human beings remain to be defined. This study aims to explore the harmful effects of AgNP on lung tissue in animals and to examine the mechanisms of protection achieved by sodium selenite.
Sprague-Dawley(SD) rats were exposed to AgNP (200 μL,1mg/mL) through a single intratracheal instillation. Sodium selenite (0.2mg/kg) was i.p. injected. Malondialdehyde (MDA) and glutathione (GSH) were measured using a spectrophotometer. Histological outcomes and ultrastructural changes were assessed by hematoxylin and eosin (HE) staining and electronic microscopy. Caspases and mitochondrial fission and fusion markers were measured by Western blotting.
The histopathologic findings showed that AgNP significantly increased the thickness of alveolar septa, accumulation of macrophage, and the formation of pulmonary bullae and pulmonary consolidation. Ultrastructural studies showed localization of AgNP inside the mitochondria, hyperplasia and vacuolation of type I and type II alveolar cells, lysis of osmiophilic lamellar bodies, and swollen of the mitochondria. AgNP elevated MDA and reduced GSH levels. AgNP activated caspases-3, increased mitochondrial fission markers Dynamin-related protein 1 (Drp1) and phospho-Drp1(p-Drp1), and decreased fusion proteins optic atrophy 1 (Opa1) and mitofusins 2 (Mfn2). Treatment with sodium selenite for 7 days corrected the AgNP-caused alterations in morphological, ultrastructural, oxidative stress, caspase-3 activation and mitochondrial dynamic imbalance.
We conclude that the exposure of AgNP causes lung tissue damage by enhances oxidative stress, activates caspases-3, and triggers mitochondrial dynamic imbalance towards fission. Sodium selenite effectively detoxifies the AgNP-induced damage to the lung tissue by preventing the above alterations.
随着纳米银（AgNP）应用的增加，其对人类健康的潜在影响仍需界定。本研究旨在探讨 AgNP 对动物肺组织的有害作用，并研究亚硒酸钠的保护机制。
通过单次气管内滴注，将 Sprague-Dawley（SD）大鼠暴露于 AgNP（200μL，1mg/mL）中。腹腔注射亚硒酸钠（0.2mg/kg）。使用分光光度计测量丙二醛（MDA）和谷胱甘肽（GSH）。通过苏木精和伊红（HE）染色和电子显微镜评估组织学结果和超微结构变化。通过 Western blot 测量半胱天冬酶和线粒体分裂和融合标志物。
组织病理学发现，AgNP 显著增加肺泡隔厚度、巨噬细胞积累、肺大疱和肺实变的形成。超微结构研究显示 AgNP 定位于线粒体内部，I 型和 II 型肺泡细胞增生和空泡化，嗜锇层状小体溶解，线粒体肿胀。AgNP 升高 MDA 并降低 GSH 水平。AgNP 激活半胱天冬酶-3，增加线粒体分裂标志物动力相关蛋白 1（Drp1）和磷酸化 Drp1（p-Drp1），并减少融合蛋白视萎缩 1（Opa1）和融合蛋白 2（Mfn2）。7 天的亚硒酸钠治疗纠正了 AgNP 引起的形态、超微结构、氧化应激、半胱天冬酶-3 激活和线粒体动力学失衡的改变。
我们得出结论，AgNP 的暴露通过增强氧化应激、激活半胱天冬酶-3 并引发线粒体向分裂的动态失衡，导致肺组织损伤。亚硒酸钠通过防止上述变化有效地解毒 AgNP 对肺组织的损伤。
