Evaluation of the effect of filtered ultrafine particulate matter on bleomycin-induced lung fibrosis in a rat model using computed tomography, histopathologic analysis, and RNA sequencing

Abstract

We aimed to investigate the effect of chronic particulate matter (PM) exposure on bleomycin-induced lung fibrosis in a rat model using chest CT, histopathologic evaluation, and RNA-sequencing. A bleomycin solution was intratracheally administrated to 20 male rats. For chronic PM exposure, after four weeks of bleomycin treatment to induce lung fibrosis, PM suspension (experimental group) or normal saline (control group) was intratracheally administrated for 10 weeks. Chest CT was carried out in all rats, and then both lungs were extracted for histopathologic evaluation. One lobe from three rats in each group underwent RNA sequencing, and one lobe from five rats in each group was evaluated by western blotting. Inflammation and fibrosis scores in both chest CT and pathologic analysis were significantly more aggravated in rats with chronic PM exposure than in the control group. Several genes associated with inflammation and immunity were also upregulated with chronic PM exposure. Our study revealed that chronic PM exposure in a bleomycin-induced lung fibrosis rat model aggravated pulmonary fibrosis and inflammation, proven by chest CT, pathologic analysis, and RNA sequencing.