PM2.5 exposures exacerbate bleomycin-induced idiopathic pulmonary fibrosis in mice by regulating ferroptosis via Nrf2/SLC7A11/GPX4 axis
- VernacularTitle:PM2.5暴露经Nrf2/SLC7A11/GPX4轴调控铁死亡加重博来霉素诱导的小鼠特发性肺纤维化
- Author:
Jin-beng DING
1
;
De-qi KONG
;
Hui-min HUANG
;
Yu GU
;
Yue-bing CHEN
;
Rui-li ZHAO
;
Su-xiao LIU
;
Xue-fang LIU
;
Ya LI
Author Information
- Publication Type:Journal Article
- Keywords: idiopathic pulmonary fibrosis; particulate matter 2.5; ferroptosis; Nrf2/SLC7A11/GPX4 axis; lipid peroxidation; ROS
- From: Chinese Pharmacological Bulletin 2025;41(2):333-339
- CountryChina
- Language:Chinese
- Abstract: Aim To explore the mechanisms of PM2.5 exposure exacerbating bleomycin(BLM)-induced idio-pathic pulmonary fibrosis(IFP)by regulating ferropto-sis via nuclear factor 2 related factor 2(Nrf2)/solute carrier family 7 member 11(SLC7A11)/glutathione peroxidase(GPX)4 axis.Methods Forty C57BL/6J mice were randomized into the control,BLM,PM2.5,BLM+PM2.5 and sulforaphane(SFN,Nrf2 agonist)groups,with eight mice in each group.PM2.5 expo-sures were conducted to the BLM-induced IPF mice for two weeks.The lung function was measured,and the content of hydroxyproline(HYP)in lung tissue and the pathomorphology of lungs were observed.Reactive oxygen species(ROS),malondialdehyde(MDA),ferrous ion(Fe2+)and glutathione(GSH)of the lung tissue were measured by ELISA.The mRNA and pro-teins levels of Nrf2,SLC7A11,GPX4,collagen typeⅠ(COL-1),α-smooth muscle actin(α-SMA)were measured by quantitative polymerase chain reaction(qPCR)and Western blot.Results Compared with the control group,the lung function of mice was signif-icantly reduced(P＜0.01)in the BLM and PM2.5 groups,while lung tissue showed the characteristic pathological changes of pulmonary fibrosis such as a large number of inflammatory cell infiltration,alveolar wall fracture,thickening,collagen deposition,and sig-nificantly increased HYP,Fe2+,ROS,MDA(P＜0.05,P＜0.01),genes and proteins of COL-1,α-SMA(P＜0.01);and decreased GSH,Nrf2,SLC7A11,GPX4 genes and proteins(P＜0.05,P＜0.01).The above-mentioned lesions were markedly aggravated in the BLM+PM2.5 group compared with the BLM(P＜0.05)and PM2.5 groups(P＜0.01),and were also improved in the SFN group(P＜0.05,P＜0.01).Conclusions PM2.5 exposures can exac-erbate IPF-induced IPF in mice,and the regulating of Nrf2/SLC7 A1 1/GPX4 axis and ferroptosis might be in-volved in the related mechanisms.
