Deciphering the Pathogenic Cascade of Acrolein-Induced Lung Injury: From Molecular Insult to Organ Failure

Acrolein, a major toxicant in fire and industrial smoke, induces fatal acute lung injury; however, its underlying mechanism remains undefined. This study aimed to elucidate this mechanism. Thirty-two SD rats were divided into four groups and exposed to acrolein via tracheal instillation at doses of 0, 0.1, 1, and 10 mg/kg, respectively. Lung function and histopathology were assessed by invasive plethysmography and H&E staining; alveolar-capillary membrane permeability, tight junction ultrastructure, and tight junction protein levels were assessed by Evans blue extravasation, transmission electron microscopy, and Western blot, respectively. Acrolein exposure triggered severe, dose-dependent impairment of pulmonary function, with significantly elevated respiratory system resistance and tissue elastance, alongside reduced inspiratory capacity and quasi-static compliance. Histological examination revealed progressive alveolar architecture disruption, inflammatory infiltration, and intra-alveolar hemorrhage across all dose groups. Evans blue assay confirmed dose-related increases in pulmonary barrier permeability. Ultrastructural analysis showed pronounced disintegration of tight junctions between endothelial and epithelial cells, correlating with acrolein concentration. Concordantly, Western blot revealed dose-dependent downregulation of claudin-18, occludin, and ZO-1. Direct disruption of alveolar tight junctions by acrolein elucidates its mechanism of inhalation toxicity and identifies this process as a potential target for barrier-stabilizing interventions.