Study On The Effects Of PM_2.5 Exposure On Ferroptosis And Pyroptosis Of Respiratory System Releated Cells

The toxic impact of particulate matter(PM_2.5)with a diameter of no more than 2.5?m on the respiratory system has become a worldwide concern.Long-term exposure to PM_2.5 can easily induce various lung-related diseases.WHO statistics and epidemiological data show that tens of thousands of people die from PM_2.5-related outdoor air pollution every year.Long-term exposure of people to PM_2.5 can cause oxidative stress,inflammation,immune abnormality,intracellular calcium ion imbalance,and energy metabolism disorders in respiratory system-related cells,while severely cause various forms of death of respiratory system-related cells.Such as apoptosis,necrosis,autophagy,aging and inflammation-mediated cell death.However,since the components of PM_2.5are related to the season and region of the sample,the mechanism and law that cause respiratory diseases are still far from being revealed.Recent reports have shown that PM_2.5 exposure to circulatory endothelial cells can cause intracellular iron overload and redox imbalance,and induce cell ferroptosis.This suggests that there may be new injury mechanisms for respiratory diseases caused by PM_2.5 exposure.And the latest research shows that ferroptosis is closely related to lung diseases including acute lung injury,chronic obstructive pulmonary disease,pulmonary fibrosis,and lung inflammation.The lung is an important organ of PM_2.5.Therefore,in order to further reveal the toxic and harmful effects of PM_2.5 exposure on the lung,this project uses 16HBE human lung bronchial cells to detect the cellular activity and iron content,GSH content,LPO and MDA production of 16HBE after PM_2.5exposure.The results of the study showed that the treatment of 16HBE cells with PM_2.5(200?g/m L)for 24 h can lead to a decrease in cell viability,an increase in cellular iron content,an increase in intracellular LPO and MDA production,and a decrease in GSH content,while the ferroptosis inhibitor DFOM(6.25?M)and Fer-1(12.50?M)can significantly reduce the toxic damage of PM_2.5to cells,inhibit the production of MDA,and reduce the loss of GSH.Morphological observations by transmission electron microscopy showed that PM_2.5 exposure induced the characteristic mitochondrial ultrastructural changes of ferroptosis in cells.The results of q PCR further indicated that the expression of the ferroptosis related genes,such as FTH1,NCOA4 and ALOX15 increased while GPX4 decreased significantly after PM_2.5exposure.The results showed that PM_2.5exposure caused ferroptosis of bronchial epithelial cells 16HBE.At the same time,the pathological core of pulmonary inflammation lies in the uncontrollable inflammatory response,but how PM_2.5 causes pulmonary uncontrollable inflammation,especially the role of macrophages in PM_2.5-induced lung gas and blood barrier damage is still unclear.At present,a way of death closely related to inflammatory reaction has come into view,that is pyroptosis.Pyroptosis is a newly discovered method of programmed cell death with extremely high pro-inflammatory properties.It is closely related to body inflammation and plays an important role in inflammation and immunity.In this study,the pyroptosis effect of human macrophages after PM_2.5exposure was confirmed by detecting the phenotypes(cell morphology,LDH level,expression of pyroptosis related proteins)induced by PM_2.5exposure.