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Updated: Dec 9, 2025
Transuterine Fetal Tracheal Occlusion Model in Mice
Published on: February 5, 2021
Nintedanib ameliorates tracheal stenosis by activating HDAC2 and suppressing IL-8 and VEGF in rabbit
Peng Wei1,2, Zhenjie Huang1, Luoman Gan3
1Department of Respiratory Medicine, The Second Affiliated Hospital of Guangxi Medical University Nanning, Guangxi, China.
Abstract:
Acquired tracheal stenosis is a common disease occurring after endotracheal intubation or tracheotomy. Currently, surgery is the main option to treat the stenosis. This study investigated therapeutic effect and possible mechanism of nintedanib on tracheal stenosis. The rabbit models of tracheal stenosis were established and were administered with nintedanib and budesonide. The damage and repair of the tracheal tissue were determined using hematoxylin and eosin (HE) staining. The expression of histone deacetylase 2 (HDAC2), interleukin-8 (IL-8) and vascular endothelial growth factor (VEGF) was detected by real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR), Western Blot and immunofluorescence assay. The expression of collagens I and III was assayed immunohistochemically. Remarkable tracheal stenosis was observed after the trachea was brushed in the rabbit model. Compared with control, the stenosis was improved after nintedanib treatment. The mRNA of HDAC2 was increased and that of IL-8 and VEGF was decreased significantly in the tracheal tissue following nintedanib treatment. Western blot analysis showed that HDAC2 increased to the level similar to that of control while VEGF remained unchanged following nintedanib treatment. Budesonide treatment also resulted in increased HDAC2 expression and decreased IL-8 and VEGF expression. Immunofluorescence assays also showed an increased HDAC2 expression following nintedanib treatment. Collagens I and III decreased significantly after nintedanib treatment in the tracheal tissues of models. Therefore, it is concluded that nintedanib alleviates the acquired tracheal stenosis by activating HDAC2 expression and suppressing IL-8 and VEGF expression, and may offer new option to medical treatment for the disease.
Insights
Nintedanib effectively treats acquired tracheal stenosis by increasing histone deacetylase 2 (HDAC2) and decreasing interleukin-8 (IL-8) and vascular endothelial growth factor (VEGF). This offers a potential new medical treatment for tracheal stenosis.
Area of Science:
- Pulmonology
- Pharmacology
- Pathology
Background:
- Acquired tracheal stenosis commonly follows endotracheal intubation or tracheotomy.
- Current primary treatment for tracheal stenosis is surgical intervention.
- Investigating novel pharmacological treatments is crucial for this condition.
Purpose of the Study:
- To evaluate the therapeutic efficacy of nintedanib in acquired tracheal stenosis.
- To elucidate the underlying molecular mechanisms of nintedanib's action.
- To compare nintedanib's effects with budesonide in a rabbit model.
Main Methods:
- Established rabbit models of acquired tracheal stenosis.
- Administered nintedanib and budesonide to assess treatment effects.
- Utilized hematoxylin and eosin (HE) staining for tissue damage assessment.
- Quantified gene and protein expression of HDAC2, IL-8, and VEGF via qRT-PCR, Western Blot, and immunofluorescence.
- Assayed collagen I and III expression using immunohistochemistry.
Main Results:
- Nintedanib treatment significantly improved tracheal stenosis in rabbit models.
- Nintedanib increased mRNA and protein expression of HDAC2.
- Nintedanib decreased mRNA expression of IL-8 and VEGF.
- Nintedanib treatment led to a significant reduction in collagen I and III deposition.
Conclusions:
- Nintedanib alleviates acquired tracheal stenosis by upregulating HDAC2 and downregulating IL-8 and VEGF.
- The drug demonstrates potential as a non-surgical therapeutic option for tracheal stenosis.
- Further research into nintedanib's mechanism could lead to improved clinical treatments.
