%0 Journal Article
%T 单壁碳纳米管的肺毒性及氧化应激机制
%A 吕高建
%A 汤莹
%A 沈亚峰
%A 雷长海
%A 赵文茹
%A 陈新
%A 杨勇骥
%J 第二军医大学学报
%D 2016
%R 10.16781/j.0258-879x.2016.07.0815
%X 目的 研究单壁碳纳米管（single-wall carbon nanotubes， SWCNTs）的肺毒性，并探讨其毒性机制，为安全生产和应用SWCNTs提供实验依据。方法 A549细胞用质量浓度为0、25、50、100、150、200μg/mL的SWCNTs溶液孵育24 h，用CCK-8和乳酸脱氢酶（lactate dehydrogenase， LDH）试剂盒分别检测SWCNTs对A549细胞活性和细胞膜的影响，Hoechst 33342和PI荧光双染法检测细胞死亡情况，透射电镜（TEM）观察细胞超微结构变化，并检测细胞内活性氧（reactive oxygen species， ROS）水平、谷胱甘肽（glutathione， GSH）浓度和超氧化物歧化酶（superoxide dismutase， SOD）活力以评估氧化应激情况。分别将0.5 mg/mL和1 mg/mL的SWCNTs溶液通过气管灌流的方法使大鼠肺部染毒，3 d后取大鼠肺脏，常规H-E染色，检测肺组织病理学变化。结果 SWCNTs对A549细胞表现出明显毒性，使细胞活性降低，死亡细胞增多，细胞膜和细胞结构损伤严重，细胞内ROS水平升高，GSH浓度和SOD活力降低。体内毒性检测结果表明SWCNTs在大鼠肺组织内积累，造成肺泡壁水肿增厚。结论 体外细胞毒性检测和动物毒性检测结果表明SWCNTs具有较大的肺毒性，其主要毒性机制是氧化应激反应。</br>Objective To systematically study the pulmonary toxicity of single-wall carbon nanotubes (SWCNTs) and to explore the related cytotoxicity mechanism, so as to provide a theoretical basis for the safe production and application of SWCNTs. Methods A549 cells were cultured in the media containing 0, 25, 50, 100, 150, and 200 μg/mL SWCNTs for 24 h, and then the cell viability and degree of cell membrane damage were assessed by CCK-8 and lactate dehydrogenase (LDH) release assay kit, respectively; the ultrastructural alteration of A549 cells was detected by transmission electron microscope (TEM). The oxidative stress response was evaluated by assessing reactive oxygen species (ROS), glutathione (GSH) and superoxide dismutase (SOD). The rats were exposed to SWCNTs by intratracheal inhalation, and then the animals were sacrificed 3 days later and the pathological sections of lung tissue were examined. Results SWCNTs showed considerable toxicity to A549 cells, decreasing cell viability, causing severe damage of cell membrane and ultrastructure, increasing the intracellular ROS level, and decreasing GSH content and SOD activity. It was found that oxidative stress is the main mechanism of SWCNTs toxicity on A549 cells. In vivo toxicity results showed that SWCNTs accumulated in the lung tissue, causing alveolar wall edema. Conclusion In vitro and in vivo toxicity results have found that SWCNTs possess a significant pulmonary toxicity, with its main toxicity mechanism being oxidative stress
%K 单壁碳纳米管 肺毒性 氧化性应激 氧化还原平衡&lt
%K /br&gt
%K single-wall carbon nanotubes pulmonary toxicity oxidative stress redox homeostasis
%U http://www.ajsmmu.cn/ajsmmu/ch/reader/view_abstract.aspx?file_no=20160170&flag=1