己酮可可碱调控芳烃受体对氯气致急性肺损伤的保护作用OACHSSCD

Objective To investigate whether pentoxifylline(PTX)exerts a protective effect on chlorine-induced acute lung injury(ALI)by regulating the aryl hydrocarbon receptor(Ahr)pathway.Methods Six male BALB/c mice were randomly divided into a control group and a chlorine group(exposed to 400 μL/L chlorine for 15 min).Lung tissues were harvested from the mice to prepare single-cell suspensions for single-cell RNA sequencing.PCA and UMAP clustering methods were used to group the cells,marker genes were used to identify cell types,and SCENIC analysis was used to infer differential expression of epithelial cell transcription factors.Inter-group visualization analysis was performed on Ahr and CYP1A1 genes.Forty male BALB/c mice were randomly divided into a control group,a chlorine group,a chlorine+PTX group,and a PTX group.The treated group received intraperitoneal injection of PTX(50 mg/kg),while the non-treated group received an equal amount of saline.After 3 h,lung function tests were performed,the degree of pathological damage in the lungs was observed using HE staining,and the activity of CYP1A1 in lung tissues was measured by ELISA.Immunohistochemistry and Western blotting were used to detect the changes in the levels of Ahr,CYP1A1,IL-6,and Occludin in lung tissues.Results After chlorine injury,HE staining showed consolidation of lung tissue and edema fluid exudation in the alveolar space.SCENIC analysis revealed increased Ahr levels in mouse lung epithelial cells,and further gene visualization suggested a correlated change in the expression of Ahr and CYP1A1 genes.PTX significantly decreased the protein levels of Ahr and IL-6(P<0.05)and significantly increased the protein level of Occludin(P<0.05).Lung function tests showed that PTX intervention increased the respiratory rate of mice,shortened the apnea time,increased the peak time ratio,and significantly improved lung function(P<0.05).Conclusion Ahr and its related signaling pathways play an important role in ALI induced by chlorine exposure.PTX may protect against chlorine-induced ALI by intervening with Ahr and reducing pulmonary inflammatory response and improving barrier function.