Role of Erythromycin-Regulated Histone Deacetylase-2 in Benign Tracheal Stenosis.

Zhenjie Huang,Luoman Gan,Tonghua Zeng,Caicheng Qin,Peng Wei,Guangnan Liu

doi:10.1155/2020/4213807

Abstract

Objective This study aims to explore the role of erythromycin-regulated histone deacetylase-2 in benign tracheal stenosis. Methods The rabbit model of tracheal stenosis was established. The rabbits were randomly divided into 8 groups. Histone deacetylase-2 (HDAC2) expression was detected by immunofluorescence. The expression of type I collagen and type III collagen was detected by immunohistochemical method. The expression of TGF-β1, VEGF and IL-8 in serum and alveolar lavage fluid was detected by ELISA. The expression of HDAC2, TGF-β1, VEGF and IL-8 in serum and alveolar lavage fluid was detected by ELISA. The expression of HDAC2, TGF-Results In Erythromycin (ERY) group, ERY + Budesonide group, ERY + Vorinostat group and ERY + Budesonide + Vorinostat group, the degree of bronchial stenosis was alleviated, and the mucosal epithelium was still slightly proliferated. The effect of ERY combined with other drugs was more obvious. The HDAC2 protein expression increased significantly in ERY group, ERY + Budesonide group and ERY + Budesonide + Vorinostat group and decreased significantly in Vorinostat group, the expression of collagen I and III decreased significantly in ERY group, ERY + Budesonide group and ERY + Budesonide + Vorinostat group (P < 0.05). The TGF-β1, VEGF and IL-8 in serum and alveolar lavage fluid was detected by ELISA. The expression of HDAC2, TGF-P < 0.05). The TGF-Conclusions Erythromycin inhibited inflammation and excessive proliferation of granulation tissue after tracheobronchial mucosal injury by up-regulating the expression of HDAC2, it promoted wound healing and alleviated tracheobronchial stenosis. When combined with budesonide, penicillin and other glucocorticoids and antibiotics, it had a good synergistic effect. However, vorinostat could attenuate erythromycin's effect by down-regulating the expression of HDAC2. It may have good clinical application prospects in the treatment of tracheal stenosis.

Highlights

Benign airway stenosis refers to a common clinical disease in which tracheal and bronchial stenosis, or even complete obstruction, results from excessive proliferation of granulation tissue in the process of repeated self-repair after longterm stimulation and injury of tracheal mucosa
Tracheal balloon dilatation is a safe, effective and economical method for the treatment of benign tracheal stenosis, the effective rate is as high as 100%, but the restenosis rate after treatment is as high as 40–70% [3]. ese patients often need repeated endoscopic interventional therapy, which significantly increases the patient’s pain, treatment
In ERY group, ERY + Budesonide group, ERY + Vorinostat group and ERY + Budesonide + Vorinostat group, the degree of bronchial stenosis was alleviated, and the mucosal epithelium was still slightly proliferated. e effect of erythromycin combined with budesonide was more obvious than that of others

Summary

Introduction

Benign airway stenosis refers to a common clinical disease in which tracheal and bronchial stenosis, or even complete obstruction, results from excessive proliferation of granulation tissue in the process of repeated self-repair after longterm stimulation and injury of tracheal mucosa. Tracheal balloon dilatation is a safe, effective and economical method for the treatment of benign tracheal stenosis, the effective rate is as high as 100%, but the restenosis rate after treatment is as high as 40–70% [3]. The reported methods for preventing and treating restenosis after endoscopic interventional therapy for tracheobronchial stenosis include local application of mitomycin C, intraluminal brachytherapy or drug-coated stent, cryotherapy and other cold interventional methods, full anti-infective therapy [4,5,6,7,8]. Low-dose erythromycin can play an anti-inflammatory role by up-regulating the activity of HDAC2 [10]

Methods

Results

Discussion

Conclusion