PM_(2.5)暴露诱发人支气管上皮细胞16HBE铁死亡

PM exposure induces ferroptosis in 16HBE human bronchial epithelial cells

为了进一步揭示PM_(2.5)暴露对肺的毒性损伤作用,本工作采用16HBE人肺支气管细胞,检测了PM_(2.5)暴露后16HBE的细胞活性、细胞中铁含量、GSH含量、LPO和MDA的产生情况.结果显示,PM_(2.5)(200μg·mL^(-1))处理16HBE细胞24 h后可导致细胞存活率下降、细胞铁含量增加、细胞内LPO和MDA生成量增加、GSH含量降低,而铁死亡抑制剂DFOM (6.25μmol·L^(-1))及Fer-1 (12.50μmol·L^(-1))可以显著减轻PM_(2.5)对细胞的毒性损伤作用,抑制MDA的产生,减少GSH的损耗.透射电子显微镜的形态学观察显示,PM_(2.5)暴露诱导细胞出现铁死亡的特征性线粒体超微结构改变,qPCR检测结果进一步提示PM_(2.5)暴露后细胞内铁死亡相关基因FTH1、NCOA4和ALOX15的表达量显著性增加,GPX4显著降低.结果说明PM_(2.5)暴露引起支气管上皮细胞16HBE发生铁死亡.

In order to reveal the toxic effects of PM_(2.5) exposure on the lungs, the levels of cell viability, iron content, GSH content, LPO and MDA production in PM_(2.5) exposed 16 HBE human lung bronchial cells were detected. The results showed that 16 HBE cells treated with PM_(2.5)(200 μg·mL^(-1))for 24 h could be led to a decrease in cell viability, an increase in cellular iron content, an increase in the production of LPO and MDA in the cell, and a decrease in GSH content. However, ferroptosis inhibitors DFOM(6.25 μmol·L^(-1)) and Fer-1(12.50 μmol·L^(-1)) could significantly reduce the toxic damage effect of PM_(2.5) on cells, inhibit the production of MDA, and reduce the loss of GSH. The morphological observation from transmission electron microscope showed that PM_(2.5) exposure induced characteristic mitochondrial ultrastructural changes of ferroptosis. The results of qPCR further indicated that the expression of the ferroptosis related genes, such as FTH1, NCOA4 and ALOX15 increased while GPX4 decreased significantly after PM_(2.5) exposure. Therefore, the results showed that PM_(2.5) exposure caused ferroptosis in 16 HBE cells.