Huang Zhenjie, Wei Peng, Gan Luoman, Li Wentao, Zeng Tonghua, Qin Caicheng, Chen Zhiyu, Liu Guangnan
Department of Respiratory Medicine, Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530007, P.R. China.
School of Medicine, Qinghai University, Xining, Qinghai 810000, P.R. China.
Exp Ther Med. 2021 May;21(5):444. doi: 10.3892/etm.2021.9872. Epub 2021 Mar 1.
The current treatments for benign tracheal stenosis are inefficient. The present study examined the expression of histone deacetylase 2 (HDAC2) in different tracheal stenosis models and explored its association with the proliferation of tracheal granulation tissue and its ability to constitute a potential therapy for tracheal stenosis. Animal tracheal stenosis models were established, as indicated by hematoxylin and eosin (H&E) staining. A total of 24 New Zealand White rabbits were randomly divided into control, erythromycin, budesonide and vorinostat groups. Stenotic tracheal tissues were collected on day 11 after drug administration for 10 days. The degree of tracheal stenosis in each group was calculated, and pathological alterations were observed using H&E staining. The mRNA expression of HDAC2, interleukin-8 (IL-8), transforming growth factor-β1 (TGF-β1) and vascular endothelial growth factor (VEGF) was examined via reverse transcription-quantitative PCR. The protein expression of HDAC2 was examined via immunofluorescence, while the expression of type I and type III collagen was assessed using immunohistochemistry. The results of the present study demonstrated that tracheal epithelial hyperplasia in the erythromycin group was improved, the degree of hyperplasia being the lowest among all groups, and tracheal stenosis was reduced compared with the control group. In the vorinostat group, tracheal epithelial tissue hyperplasia was aggravated and stenosis was increased. The HDAC2 mRNA and protein levels were increased and decreased in the erythromycin and vorinostat groups, respectively. In contrast, the IL-8 mRNA expression levels were decreased and increased in the erythromycin and vorinostat groups, respectively. TGF-β1, VEGF, type I and type III collagen expression was decreased in the erythromycin group, while TGF-β1, VEGF and type III collagen expression was increased in the vorinostat group. Compared with the control, the budesonide group did not exhibit any alterations in all of the indicators examined, including TGF-β1, VEGF, IL-8, HDAC2 and collagen. Erythromycin treatment upregulated the expression of HDAC2, inhibited the inflammatory responses and reduced the proliferation of tracheal granulation tissue. In contrast, vorinostat treatment downregulated HDAC2 expression, promoted the inflammatory responses and increased the proliferation of tracheal granulation tissue. These results suggest that regulating HDAC2 may be used as a potential treatment for benign tracheal stenosis.
目前针对良性气管狭窄的治疗方法效果不佳。本研究检测了组蛋白去乙酰化酶2（HDAC2）在不同气管狭窄模型中的表达，并探讨其与气管肉芽组织增殖的关系以及构成气管狭窄潜在治疗方法的能力。通过苏木精-伊红（H&E）染色建立动物气管狭窄模型。将24只新西兰白兔随机分为对照组、红霉素组、布地奈德组和伏立诺他组。给药10天后，于第11天收集狭窄气管组织。计算每组气管狭窄程度，并用H&E染色观察病理改变。通过逆转录-定量PCR检测HDAC2、白细胞介素-8（IL-8）、转化生长因子-β1（TGF-β1）和血管内皮生长因子（VEGF）mRNA的表达。通过免疫荧光检测HDAC2蛋白表达，用免疫组织化学评估Ⅰ型和Ⅲ型胶原蛋白的表达。本研究结果表明，红霉素组气管上皮增生得到改善，增生程度在所有组中最低，与对照组相比气管狭窄减轻。在伏立诺他组中气管上皮组织增生加重，狭窄增加。HDAC2 mRNA和蛋白水平在红霉素组中升高，在伏立诺他组中降低。相反，IL-8 mRNA表达水平在红霉素组中降低，在伏立诺他组中升高。红霉素组中TGF-β1、VEGF、Ⅰ型和Ⅲ型胶原蛋白表达降低，而伏立诺他组中TGF-β1、VEGF和Ⅲ型胶原蛋白表达升高。与对照组相比，布地奈德组在所有检测指标（包括TGF-β1、VEGF、IL-8、HDAC2和胶原蛋白）中均未表现出任何改变。红霉素治疗上调了HDAC2的表达，抑制了炎症反应并减少了气管肉芽组织的增殖。相反，伏立诺他治疗下调了HDAC2表达，促进了炎症反应并增加了气管肉芽组织的增殖。这些结果表明，调节HDAC2可能用作良性气管狭窄的潜在治疗方法。
