Fine particulate matter induces airway hyper-responsiveness by up-regu-lating muscarinic M3 receptor in mice
10.3969/j.issn.1000-4718.2025.04.009
- VernacularTitle:细颗粒物通过上调毒蕈碱M3受体诱导小鼠气道高反应性
- Author:
Rong WANG
1
;
Nana WANG
1
;
Kuan YANG
1
;
Lili YU
1
;
Bei QIN
1
Author Information
1. 西安市多靶协同抗高血压创新药物研制重点实验室,西安市智创抗高血压药物国际科技合作基地,西安医学院药物研究所,西安医学院药学院,陕西 西安 710021
- Publication Type:Journal Article
- Keywords:
fine particulate matter;
airway hyper-responsiveness;
muscarinic receptors;
mitogen-activated protein kinase pathway
- From:
Chinese Journal of Pathophysiology
2025;41(4):696-703
- CountryChina
- Language:Chinese
-
Abstract:
AIM:Fine particulate matter(PM2.5)is closely associated with airway hyper-responsiveness(AHR).However,the underlying mechanism by which PM2.5 leads to AHR is still unclear.This study aimed to investi-gate the respiratory effects of ambient PM2.5 exposure.METHODS:Forty mice were randomly divided into five groups:control group(intranasal saline),lipopolysaccharide(LPS)group(100 mg/L),PM2.5 low-dose group(0.003 5 mg/d),PM2.5 medium-dose group(0.007 mg/d),and PM2.5 high-dose group(0.014 mg/d).They were treated with intranasal in-stillation for 30 d.Lung function and tracheal contractile responses were evaluated using whole-body plethysmography and sensitive wire myograph.Inflammatory mediators in serum and oxidative stress parameters were detected using enzyme-linked immunosorbent assay(ELISA).Lung tissues were subjected to HE and Masson staining.RT-qPCR and Western blot were used to determine the expression of contractile receptors and the phosphorylation of the mitogen-activated protein kinase(MAPK)signal pathway.RESULTS:Intranasal instillation of PM2.5 significantly increased airway resistance in mice and enhanced tracheal contractility in response to carbachol.PM2.5 elevated levels of tumor necrosis factor-α(TNF-α),interleukin(IL)-1β,and IL-6 in serum.PM2.5 instillation also led to a decrease in glutathione peroxidase(GSH-Px)levels and an increase in malondialdehyde(MDA)levels.Lung tissue exhibited notable pathological changes,including inflammatory cell infiltration,hyperplasia of alveolar epithelial cells,and collagen deposition.Mechanistically,exposure to PM2.5 increased the expression of muscarinic M3 receptor mRNA and protein,as well as the phosphorylation of p-ERK1/2 and p-p38 proteins following PM2.5 instillation.CONCLUSION:Intranasal instillation of PM2.5 induced inflammation and oxidative stress,along with the activation of the extracellular signal-regulated kinase 1/2(ERK1/2)and p38 MAPK pathways,resulting in the upregulation of M3 receptor-induced AHR.
