Clinical, Histological, and Profibrotic Extracellular Matrix Protein Changes in a Model of Tracheal Stenosis Induced by Cervical Tracheal Autotransplantation

Abstract

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 (TGFβ), fibronectin (FN), elastin (ELN), integrin β1 (ITGβ1), 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, TGFβ1, TGFβ2, FN, ELN, and ITGβ1, and mild expression of TGFβ3 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 (TGFβ1, TGFβ2, collagen, FN, ELN, ITGβ1) and downregulation of antifibrotic proteins (TGFβ3, MMP1). Therefore, this model may be used to test new pharmacological treatments for reversing or preventing TS, and conduct basic studies regarding its pathophysiology.

Keywords

• tracheal stenosis
• animal model
• bleomycin
• tgfβ
• extracellular matrix protein