聚苯乙烯纳塑料诱导Caco-2细胞氧化应激和线粒体损伤的研究
Polystyrene Nanoplastics Induce Oxidative Stress and Mitochondrial Damage in Caco-2 Cells
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摘要: 微/纳米塑料的潜在毒理效应及健康风险引起广泛关注。本研究以人结直肠腺癌细胞(Caco-2)为模型，研究聚苯乙烯纳米塑料(polystyrene nanoparticles, PS-NPs)的细胞毒性，从氧化应激和线粒体损伤角度探讨PS-NPs肠道毒性机制。结果表明PS-NPs暴露导致细胞形态改变，细胞活力下降，乳酸脱氢酶释放增加，确定其最低效应浓度是50 μg·mL-1。随着PS-NPs暴露浓度增加，细胞活性氧(reactive oxygen species, ROS)含量和丙二醛水平升高，线粒体膜电位水平降低、Ca2+超载、线粒体膜通透性转换孔开放、二磷酸腺苷/三磷酸腺苷比率(ADP/ATP)上升，最终细胞凋亡率增加。PS-NPs暴露浓度为200 μg·mL-1时，ROS含量升高至对照组的3.85倍；线粒体去极化程度降低至对照组的0.63倍；细胞凋亡率达到28.90%(P＜0.01)。PS-NPs通过诱导细胞ROS生成，产生氧化应激，过量的ROS会对线粒体造成损伤，最终导致细胞凋亡率升高，因此氧化应激和线粒体损伤是PS-NPs引起细胞毒性的关键机制。本研究结果将为PS-NPs的肠道毒理效应和健康风险评估提供基础数据和科学依据。Abstract: The potential toxicological effects and health risks of micro/nano plastics have attracted widespread attention. In this study, human colorectal adenocarcinoma cells (Caco-2) were used as a model to investigate the cytotoxicity of PS-NPs and explore the potential intestinal toxicity mechanisms based on oxidative stress and mitochondrial damage. Our results showed that the exposure to PS-NPs led to changes in cell morphology, decreased cell viability, and increased release of lactate dehydrogenase. The minimum effective concentration of PS-NPs was determined at 50 μg·mL-1. With the increase of concentration of PS-NPs, the cellular reactive oxygen species (ROS) content and malondialdehyde level increased, the mitochondrial membrane potential level decreased, Ca2+ overload occurred, the mitochondrial membrane permeability transition pore opened, the ratio adenosine diphosphate/adenosine triphosphate (ADP/ATP) increased, and finally the cell apoptosis rate increased. When cells were exposed to 200 μg·mL-1 of PS-NPs, the ROS content was elevated to 3.85-fold and the mitochondrial depolarisation was reduced to 0.63-fold than that of the control group. Meanwhile, the cell apoptosis rate reached 28.90% (P<0.01). Taken together, the exposure to PS-NPs induced the cellular ROS generation, and the excess ROS gave rise to the mitochondrial damage, which in turn led to the increased cell apoptosis rate. Our study provides basic data and scientific basis for the intestinal toxicological effects and health risk assessment of PS-NPs.
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Key words:
- nanoparticles /
- Caco-2 cells /
- oxidative stress /
- mitochondrial damage /
- apoptosis
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