The profibrotic effects of chronic microaspiration of bile acids on lungs of rats at different stages

•Dynamic changes in rat models after bile acid microaspiration at different stages.•Lung fibrosis developed after bile acid microaspiration in a time-dependent way.•The mechanism likely involved TGF-β1, oxidative stress, and FXR related pathways.•The bile acid microaspiration rat model may provide a useful tool for IPF research. This study aimed to explore the profibrotic effects of chronic microaspiration of two major bile acids, including chenodeoxycholic acid (CDCA) and deoxycholic acid (DCA), on lungs of rats at different stages, as well as the underlying mechanisms in vivo. A rat model was induced by weekly intratracheal instillation of DCA and CDCA. Our results showed that chronic microaspiration of bile acids resulted in alveolar structure disorder, and inflammatory cells infiltration in the pulmonary interstitium at the early stage. Subsequently, numerous fibroblasts were proliferated, and collagen deposition was profoundly increased over the interstitium of the airways and vessels. Compared with control group, the expression of α-smooth muscle actin, type I collagen, hydroxyproline, transforming growth factor-β1 (TGF-β1), and matrix metalloproteinase-9 in the lung tissues were remarkably elevated at the 2nd week, reached the highest level at the 6th week, and maintained high at the 8th week in both DCA- and CDCA-treated groups (P