环境与职业医学2025，Vol.42Issue(8)：971-977,1002,8.DOI:10.11836/JEOM24605
铁死亡在亚慢性染毒苯并[a]芘诱发小鼠肺组织细胞损伤中的作用研究
Subchronic exposure to benzo[a]pyrene results in lung tissue cell damage caused by ferroptosis in mice
摘要
Abstract
[Background]Exposure to benzo[a]pyrene(BaP)may impair lung function through various mechanisms;however,it remains uncertain whether BaP induces ferroptosis in lung tissue cells,resulting in lung function impairment. [Objective]To investigate the ferroptosis of lung tissue cells triggered by subchronic BaP exposure in mice and its correlation with lung injury,and to explore the function of ferroptosis in BaP-induced lung tissue damage. [Method]Seventy-two healthy 3-weeks-old male C57BL/6J mice were acclimatized for 1 week and then randomly divided into six groups:control group(corn oil 10 mL·kg-1),low-dose BaP group(2.5 mg·kg-1),medium-dose BaP group(5 mg·kg-1),high-dose BaP group(10 mg·kg-1),BaP+ferrostatin-1(Fer-1)group(10 mg·kg-1+1 mg·kg-1),and Fer-1 group(1 mg·kg-1),with 12 mice each group.Corn oil and BaP were administered via gavage every other day,followed by an intraperitoneal injection of Fer-1 the subsequent day,throughout a period of 90 d.Whole-body plethysmography was applied to detect lung function;hematoxylin-eosin staining(HE)and Masson staining were used to observe lung tissue injury and fibrosis;microscopy of alveolar epithelial cells was conducted to reveal mitochondrial mor-phology;biochemical assays were used to measure the content of tissue iron,malondialdehyde(MDA),and glutathione(GSH),as well as the activity of glutathione peroxidase(GSH-Px);Western blotting and real-time quantitative PCR(RT-qPCR)analyses were performed to reveal the protein and mRNA expression of ferroptosis markers. [Results]Compared to the control group,the high-dose BaP group showed a significant increase in expiration time(Te)(P<0.01),and a significant decrease in ratio rate of achieving peak expiratory flow(Rpef),tidal volume(TVb),peak inspiratory flow(PIF),minute volume(MVb),and peak expiratory flow(PEF)(P<0.05 or 0.01).Based on the results of HE and Masson staining,partial destruction of alveolar structures,thickening of alveolar walls,infiltration of inflammatory cells,significant thickening of tracheal walls and a large deposition of collagen fibers in lung tissue were observed in the medium-and high-dose BaP groups.By microscopy,the alveolar epithelial cells exposed to low-dose BaP showed condensed chromatin,and the mitochondria exposed to medium and high-dose BaP showed wrinkles,increased mitochondrial membrane density,and diminished mitochondrial cristae.Compared to the control group,in the medium-and high-dose BaP groups,the lung tissue iron content and the expression levels of ACSL4 protein and mRNA significantly elevated(P<0.01 or 0.05),while the mRNA expression level of SLC7A11 significantly decreased(P<0.05);in the high-dose BaP group,the MDA content,COX2 pro-tein,and PTGS2 mRNA expression levels significantly increased(P<0.05 or 0.01),GSH content and GSH-Px activity,GPX4 protein and mRNA expression levels,and the expression level of SLC7A11 protein significantly decreased(P<0.01 or 0.05).The ferroptosis inhibitor Fer-1 markedly reversed respiratory function,morphology,mitochondrial alterations,and the aforementioned ferroptosis-related biochemical indicators. [Conclusion]Subchronic exposure to BaP can induce ferroptosis in mice lung tissue cells,resulting in compromised lung function.关键词
苯并[a]芘/亚慢性染毒/肺功能/铁死亡Key words
benzo[a]pyrene/subchronic exposure/lung function/ferroptosis分类
预防医学引用本文复制引用
周潮丽,丁诗涵,何慧,马智瑞,陈洁,郭星笛,吕懿,郑金平..铁死亡在亚慢性染毒苯并[a]芘诱发小鼠肺组织细胞损伤中的作用研究[J].环境与职业医学,2025,42(8):971-977,1002,8.基金项目
山西省自然科学基金项目(202203021211106) （202203021211106）
山西省"1331工程"项目(2021-5-2-2-B1) （2021-5-2-2-B1）
长治医学院创新团队项目(CX202001) （CX202001）
