Clinical, Histological, and Profibrotic Extracellular Matrix Protein Changes in a Model of Tradieal stenosis Induced by Cervical Tracheal Autotranspiantation

Background: Tracheal stenosis (TS) is a complication of prolonged intubation, tracheotomy, and tracheal surgery that compromises the vascular supply. Animal models are essential for studying its pathophysiology and the effect of interventions. Objective: To establish a TS model in rats secondary to tracheal autotransplantation with a graft submerged in bleomycin (Atx-Bleo). Additionally, to evaluate the clinical and histological changes, as well as the expression of newly formed collagen (NFC), isoforms of transforming growth factor beta (TGF beta), fibronectin (FN), elastin (ELN), integrin beta 1 (ITG beta 1), and matrix metalloproteinase 1 (MMP1) in TS. Methods: Twenty Wistar rats were divided into three groups: group I (n = 20) control; group II (n = 10) end-to-end anastomosis of the trachea (tracheoplasty); and group III (n = 10) Atx-Bleo. The animals were evaluated clinically, tomographically, macroscopically, morphometrically, and microscopically. NFC deposition, and the expression of profibrotic and antifibrotic proteins were evaluated in tracheal scars. Results: All animals survived the surgical procedure and the study period. Compared with the other study groups, the Atx-Bleo group developed TS and fibrosis, exhibited higher expression of NFC, TGF beta 1, TGF beta 2, FN, ELN, and ITG beta 1, and mild expression of TGF beta 3 and MMP1 (p < 0.005; analysis of variance, Dunnett and Tukey tests). Conclusion: Atx-Bleo in TS model rats produces tomographic and histological changes, and induces the upregulation of profibrotic proteins (TGF beta 1, TGF beta 2, collagen, FN, ELN, ITG beta 1) and downregulation of antifibrotic proteins (TGF beta 3, MMP1). Therefore, this model may be used to test new pharmacological treatments for reversing or preventing TS, and conduct basic studies regarding its pathophysiology.