聚苯乙烯微塑料对人肾近端肾小管上皮细胞 HK-2 和雄性 C57BL/6 小鼠的肾脏相关影响。
The Kidney-Related Effects of Polystyrene Microplastics on Human Kidney Proximal Tubular Epithelial Cells HK-2 and Male C57BL/6 Mice.
机构信息
Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
Department of Cosmeceutics, China Medical University, Taichung, Taiwan.
出版信息
Environ Health Perspect. 2021 May;129(5):57003. doi: 10.1289/EHP7612. Epub 2021 May 6.
BACKGROUND
Understanding the epidemic of chronic kidney disease of uncertain etiology may be critical for health policies and public health responses. Recent studies have shown that microplastics (MPs) contaminate our food chain and accumulate in the gut, liver, kidney, muscle, and so on. Humans manufacture many plastics-related products. Previous studies have indicated that particles of these products have several effects on the gut and liver. Polystyrene (PS)-MPs (PS-MPs) induce several responses, such as oxidative stress, and affect living organisms.
OBJECTIVES
The aim of this study was to investigate the effects of PS-MPs in kidney cells and .
METHODS
PS-MPs were evaluated in human kidney proximal tubular epithelial cells (HK-2 cells) and male C57BL/6 mice. Mitochondrial reactive oxygen species (ROS), endoplasmic reticulum (ER) stress, inflammation, and autophagy were analyzed in kidney cells. , we evaluated biomarkers of kidney function, kidney ultrastructure, muscle mass, and grip strength, and urine protein levels, as well as the accumulation of PS-MPs in the kidney tissue.
RESULTS
Uptake of PS-MPs at different concentrations by HK-2 cells resulted in higher levels of mitochondrial ROS and the mitochondrial protein Bad. Cells exposed to PS-MPs had higher ER stress and markers of inflammation. MitoTEMPO, which is a mitochondrial ROS antioxidant, mitigated the higher levels of mitochondrial ROS, Bad, ER stress, and specific autophagy-related proteins seen with PS-MP exposure. Furthermore, cells exposed to PS-MPs had higher protein levels of LC3 and Beclin 1. PS-MPs also had changes in phosphorylation of mitogen-activated protein kinase (MAPK) and protein kinase B (AKT)/mitogen-activated protein kinase (mTOR) signaling pathways. In an study, PS-MPs accumulated and the treated mice had more histopathological lesions in the kidneys and higher levels of ER stress, inflammatory markers, and autophagy-related proteins in the kidneys after PS-MPs treatment by oral gavage.
CONCLUSIONS
The results suggest that PS-MPs caused mitochondrial dysfunction, ER stress, inflammation, and autophagy in kidney cells and accumulated in HK-2 cells and in the kidneys of mice. These results suggest that long-term PS-MPs exposure may be a risk factor for kidney health. https://doi.org/10.1289/EHP7612.
背景
了解病因不明的慢性肾病的流行情况可能对卫生政策和公共卫生应对至关重要。最近的研究表明，微塑料（MPs）污染了我们的食物链，并在肠道、肝脏、肾脏、肌肉等部位积累。人类制造了许多与塑料相关的产品。先前的研究表明，这些产品的颗粒对肠道和肝脏有多种影响。聚苯乙烯（PS）-MPs（PS-MPs）诱导氧化应激等多种反应，影响生物体。
目的
本研究旨在探讨 PS-MPs 在肾细胞中的作用。
方法
在人肾近端管状上皮细胞（HK-2 细胞）和雄性 C57BL/6 小鼠中评估 PS-MPs。分析肾细胞中的线粒体活性氧（ROS）、内质网（ER）应激、炎症和自噬。在动物研究中，我们评估了肾功能生物标志物、肾脏超微结构、肌肉质量和握力、尿液蛋白水平以及 PS-MPs 在肾脏组织中的积累。
结果
HK-2 细胞摄取不同浓度的 PS-MPs 导致线粒体 ROS 和线粒体蛋白 Bad 水平升高。暴露于 PS-MPs 的细胞 ER 应激和炎症标志物水平升高。线粒体 ROS 抗氧化剂 MitoTEMPO 减轻了 PS-MP 暴露引起的线粒体 ROS、Bad、ER 应激和特定自噬相关蛋白水平升高。此外，暴露于 PS-MPs 的细胞 LC3 和 Beclin 1 的蛋白水平升高。PS-MPs 还改变了丝裂原活化蛋白激酶（MAPK）和蛋白激酶 B（AKT）/丝裂原活化蛋白激酶（mTOR）信号通路的磷酸化。在一项动物研究中，PS-MPs 蓄积，经口灌胃 PS-MPs 处理后，小鼠肾脏出现更多组织病理学损伤，肾脏 ER 应激、炎症标志物和自噬相关蛋白水平升高。
结论
结果表明，PS-MPs 导致肾细胞中线粒体功能障碍、内质网应激、炎症和自噬，并在 HK-2 细胞和小鼠肾脏中蓄积。这些结果表明，长期 PS-MPs 暴露可能是肾脏健康的一个风险因素。https://doi.org/10.1289/EHP7612.
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