基于Caco-2细胞单层模型的二硫化钨纳米材料肠毒性研究  

Intestinal toxicity of tungsten disulfide nanosheet determined by Caco-2 cell monolayer model

作　　者：顾纬卿 吴小梅 刘苏 吴兵[1] GU Weiqing;WU Xiaomei;LIU Su;WU Bing(State Key Laboratory of Pollution Control and Resource Reuse,School of the Environment,Nanjing University,Nanjing 210023;Department of Environmental Science,School of Engineering,China Pharmaceutical University,Nanjing 211198)

机构地区：[1]南京大学环境学院,污染控制与资源化研究国家重点实验室,南京210023 [2]中国药科大学工学院环境科学科研室,南京211198

出　　处：《环境科学学报》2021年第5期2039-2046,共8页Acta Scientiae Circumstantiae

基　　金：国家自然科学基金项目(No.21577061,21806078);国家重点研发计划项目课题(No.2016YFA0203103)。

摘　　要：二硫化钨纳米材料(WS_(2))因其独特的晶体结构和机械柔韧性,在电子、能源和医药等领域应用前景广阔,但其毒性危害也受到广泛关注,本研究采用人结肠癌Caco-2细胞构建了体外肠道吸收模型,研究了WS_(2)纳米片对肠道细胞层结构和功能的毒性效应.结果表明,1~80μg·mL^(-1) WS_(2)未诱导Caco-2细胞内线粒体膜电位的改变,≥50μg·mL^(-1) WS_(2)增加了胞内氧化自由基含量,具有低细胞毒性.对于Caco-2细胞单层模型,2和20μg·mL^(-1) WS_(2)纳米片均不能改变其渗透性和完整性,未引起氧化应激相关基因表达的变化,但抑制了细胞膜ABC转运蛋白的活性.WS_(2)纳米片与镉、砷和苯并(a)芘等污染物共暴露于Caco-2细胞单层时,细胞膜损伤和细胞单层转运功能未被改变,但增加了镉对Caco-2细胞单层氧化应激相关基因GPx和OXSR1表达水平的影响.研究结果为WS_(2)纳米片的胃肠道毒性评估及健康风险评价提供了数据支撑.Tungsten disulfide(WS_(2)) as a two-dimensional nanomaterial has a broad application prospect in the fields of electronics, energy and medicine due to its unique crystal structure and mechanical flexibility. In this paper, human colon cancer Caco-2 cells were used to construct an in vitro intestinal absorption model, and the toxic effects of WS_(2) on intestinal cell layer structure and function were studied. Results showed that 1~80 μg·mL^(-1) WS_(2) did not induce the change of mitochondrial membrane potential in the Caco-2 cells, and ≥ 50 μg·mL^(-1) WS_(2) increased the content of intracellular reactive oxygen species, showing low cytotoxicity. For the monolayer of Caco-2 cells, 2 and 20 μg·mL^(-1) WS_(2) did not change their permeability, integrity, and expression of genes related to oxidative stress. However, WS_(2) inhibited the activity of plasma membrane ABC transporter in the Caco-2 cell monolayer. When the WS_(2) were co-exposed to the Caco-2 cell monolayer with cadmium, arsenic, benzo(a)pyrene, the cell membrane integrity and monolayer transport function in the monolayer did not change, however, the influence of cadmium on the expressions of oxidative stress-related genes GPx and OXSR1 in the cell monolayer increased. Results of this study provide basic data for the evaluation of gastrointestinal toxicity and health risk of WS_(2).

关 键 词：二硫化钨 肠毒性 CACO-2细胞 联合毒性 

分 类 号：X171.5[环境科学与工程—环境科学]