Expression of HDAC2 in tracheal granulation tissue and its relationship with tracheal stenosis in animal model of tracheal stenosis_Chinese Journal of Respiratory and Critical Care Medicine

Authors：

GAN Jinghua ¹ , GAN Luoman ² , QIN Enyuan ¹ , MENG Xiaoyan ³ , LI Yu ¹ , LI Wentao ¹ , HOU Changchun ¹ , ZHOU Lei ¹ ,  LIU Guangnan ¹

1. Department of Respiratory Medicine, Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530007, P. R. China;
2. Qinghai University School of Medicine, Xining, Qinghai 810016, P. R. China;
3. Liuzhou Workers Hospital, Liuzhou, Guangxi 545005, P. R. China;

Corresponding author：

LIU Guangnan, Email: gnliu63@hotmail.com

Keywords：

Benign tracheal stenosis; Histone deacetylase 2; Erythromycin; Infection; Inflammation

DOI：

10.7507/1671-6205.201711042

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ObjectiveTo investigate the expression of histone deacetylase 2 (HDAC2) in animal model of benign tracheal stenosis, and explore the mechanism of HDAC2 in development of tracheal stenosis.MethodsEighteen rabbits were randomly divided into a blank control group, a model group, and an erythromycin group, with 6 rats in each group. The model group and the erythromycin group underwent tracheostomy, the inner wall of trachea was brushed back and forth with a nylon brush for more than 20 times to induce benign tracheal stenosis. From 7 days before surgery to 9 days after surgery, the model group received gavage with saline, the erythromycin group received gavage with low-dose erythromycin in dose of 15 mg·kg^–1·d^–1, and the control group did not receive any treatment. On the 10^th day after operation, all the rabbits were sacrificed and the trachea was cut to measure the tracheal stenosis. RNA and protein were extracted from the granulation tissue in the stenosis and the relative mRNA expressions of HDAC2, interleukin (IL)-6 and IL-8 in the granulation tissue were detected by real-time fluorescence quantitative PCR. The relative expression of HDAC2 protein was detected by Western blot.ResultsCompared with the blank control group, the tracheal stenosis in the model group was more obvious [(84.60±1.14)% vs.(27.00±6.44)%], the mRNA and protein expressions of HDAC2 were decreased (0.29±0.07 vs. 1.00±0.00, 0.20±0.02 vs. 0.49±0.04), the mRNA expressions of IL-6 and IL-8 were up-regulated (4.22±0.67 vs. 1.00±0.00, 162.72±23.23 vs.1.00±0.00). Compared with the model group, tracheal stenosis in the erythromycin group was relieved [(64.00±12.25)% vs. (84.60±1.14)%], the mRNA and protein expressions of HDAC2 were increased (0.42±0.14 vs. 0.29±0.07, 0.43±0.01 vs. 0.20±0.02), the mRNA expressions of IL-6 and IL-8 were decreased (0.72±0.24 vs. 4.22±0.67, 130.22±7.93 vs. 162.72±23.23). All the differences were statistically significant (all P<0.05). The Pearson correlation coefficient between tracheal stenosis and HDAC2 mRNA relative expression was –0.96 (P<0.05).ConclusionsThe down-regulation of HDAC2 expression in model of benign tracheal stenosis is related to the occurrence and development of tracheal stenosis. The low dose of erythromycin may be used to treat benign tracheal stenosis by up-regulating expression of HDAC2 and thus inhibiting the inflammatory disorder during tracheal injury repair.

Citation： GAN Jinghua, GAN Luoman, QIN Enyuan, MENG Xiaoyan, LI Yu, LI Wentao, HOU Changchun, ZHOU Lei, LIU Guangnan. Expression of HDAC2 in tracheal granulation tissue and its relationship with tracheal stenosis in animal model of tracheal stenosis. Chinese Journal of Respiratory and Critical Care Medicine, 2018, 17(3): 285-289. doi: 10.7507/1671-6205.201711042 Copy

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2.	吴旋, 苏振忠, 胡丽茎, 等. 560 例气管切开行机械通气患者并发气管狭窄的危险因素分析. 中华耳鼻咽喉头颈外科杂志, 2007, 42(11): 839-842.
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7.	宋岩, 杨静, 季文樾. 大耳白兔气管切开术后炎症及机械损伤导致气管狭窄的实验研究. 中国医科大学学报, 2009, 38(1): 50-51, 59.
8.	李莉华, 黎雨, 甘罗曼, 等. 静脉用抗菌素对良性气管狭窄呼吸内镜介入治疗术后长期疗效的影响. 国际呼吸杂志, 2017, 37(15): 1154-1160.
9.	López-Boado YS, Rubin BK. Macrolides as immunomodulatory medications for the therapy of chronic lung diseases. Curr Opin Pharmacol, 2008, 8(3): 286-291.
10.	Seemungal TA, Wilkinson TM, Hurst JR, et al. Long-term erythromycin therapy is associated with decreased chronic obstructive pulmonary disease exacerbations. Am J Respir Crit Care Med, 2008, 178(11): 1139-1147.
11.	Blasi F, Mantero M, Aliberti S. Antibiotics as immunomodulant agents in COPD.Curr Opin Pharmacol, 2012, 12(3): 293-299.
12.	Friedlander AL, Albert RK. Chronic macrolide therapy in inflammatory airways diseases. Chest, 2010, 138(5): 1202-1212.
13.	Yatsunami J, Tsuruta N, Hara N, et al. Inhibition of tumor angiogenesis by roxithromycin, a 14-membered ring macrolide antibiotic. Cancer Letters, 1998, 131(2): 137-143.
14.	He ZY, Ou LM, Zhang JQ, et al. Effect of 6 months of erythromycin treatment on inflammatory cells in induced sputum and exacerbations in chronic obstructive pulmonary disease. Respiration, 2010, 80(6): 845-852.
15.	牛卉, 梅和坤, 胡雪栋, 等. 红霉素长期小剂量超说明书用药的文献计量分析. 中国临床药理学杂志, 2015, (3): 223-226.
16.	Yao H, Rahman I. Current concepts on oxidative/carbonyl stress, inflammation and epigenetics in pathogenesis of chronic obstructive pulmonary disease. Toxicol Appl Pharmacol, 2011, 254(2): 72-85.
17.	Adenuga D, Yao H, March TH, et al. Histone deacetylase 2 is phosphorylated, ubiquitinated, and degraded by cigarette smoke. Am J Respir Cell Mol Biol, 2009, 40(4): 464-473.
18.	Bhavsar P, Ahmad T, Adcock IM. The role of histone deacetylases in asthma and allergic diseases.J Allergy Clin Immunol, 2008, 121(3): 580-584.
19.	Ito K, Hanazawa T, Tomita K, et al. Oxidative stress reduces histone deacetylase 2 activity and enhances IL-8 gene expression: role of tyrosine nitration. Biochem Biophys Res Commun, 2004, 315(1): 240-245.
20.	Marwick JA, Kirkham PA, Stevenson CS, et al. Cigarette smoke alters chromatin remodeling and induces proinflammatory genes in rat lungs. Am J Respir Cell Mol Biol, 2004, 31(6): 633-642.
21.	Guven M, Turan F, Eyibilen A, et al. A comparison of the efficacy of 5-fluorouracil/triamcinolone, carnitine and dexamethasone therapy on wound healing in tracheal injury: potential for preventing tracheal stenosis? Eur Arch Otorhinolaryngol, 2012, 269(1): 201-206.

1. Nouraei SA, Ma E, Patel A, et al. Estimating the population incidence of adult post-intubation laryngotracheal stenosis. Clin Otolaryngol, 2007, 32(5): 411-412.
2. 吴旋, 苏振忠, 胡丽茎, 等. 560 例气管切开行机械通气患者并发气管狭窄的危险因素分析. 中华耳鼻咽喉头颈外科杂志, 2007, 42(11): 839-842.
3. 李莉华, 徐明鹏, 甘罗曼, 等.小剂量红霉素对气管损伤后肉芽组织增生的影响. 中华医学杂志, 2017, 97(10): 777-781.
4. 李梅华, 钟小宁, 文明智, 等.红霉素对香烟烟雾刺激的人巨噬细胞组蛋白去乙酰化酶 2 表达降低的抑制作用. 国际呼吸杂志, 2014. 34(18): 1383-1387.
5. Nakagishi Y, Morimoto Y, Fujita M, et al. Rabbit model of airway stenosis induced by scraping of the tracheal mucosa. Laryngoscope, 2005, 115(6): 1087-1092.
6. Mazhar K, Gunawardana M, Webster P, et al. Bacterial biofilms and increased bacterial counts are associated with airway stenosis. Otolaryngol Head Neck Surg, 2014, 150(5): 834-840.
7. 宋岩, 杨静, 季文樾. 大耳白兔气管切开术后炎症及机械损伤导致气管狭窄的实验研究. 中国医科大学学报, 2009, 38(1): 50-51, 59.
8. 李莉华, 黎雨, 甘罗曼, 等. 静脉用抗菌素对良性气管狭窄呼吸内镜介入治疗术后长期疗效的影响. 国际呼吸杂志, 2017, 37(15): 1154-1160.
9. López-Boado YS, Rubin BK. Macrolides as immunomodulatory medications for the therapy of chronic lung diseases. Curr Opin Pharmacol, 2008, 8(3): 286-291.
10. Seemungal TA, Wilkinson TM, Hurst JR, et al. Long-term erythromycin therapy is associated with decreased chronic obstructive pulmonary disease exacerbations. Am J Respir Crit Care Med, 2008, 178(11): 1139-1147.
11. Blasi F, Mantero M, Aliberti S. Antibiotics as immunomodulant agents in COPD.Curr Opin Pharmacol, 2012, 12(3): 293-299.
12. Friedlander AL, Albert RK. Chronic macrolide therapy in inflammatory airways diseases. Chest, 2010, 138(5): 1202-1212.
13. Yatsunami J, Tsuruta N, Hara N, et al. Inhibition of tumor angiogenesis by roxithromycin, a 14-membered ring macrolide antibiotic. Cancer Letters, 1998, 131(2): 137-143.
14. He ZY, Ou LM, Zhang JQ, et al. Effect of 6 months of erythromycin treatment on inflammatory cells in induced sputum and exacerbations in chronic obstructive pulmonary disease. Respiration, 2010, 80(6): 845-852.
15. 牛卉, 梅和坤, 胡雪栋, 等. 红霉素长期小剂量超说明书用药的文献计量分析. 中国临床药理学杂志, 2015, (3): 223-226.
16. Yao H, Rahman I. Current concepts on oxidative/carbonyl stress, inflammation and epigenetics in pathogenesis of chronic obstructive pulmonary disease. Toxicol Appl Pharmacol, 2011, 254(2): 72-85.
17. Adenuga D, Yao H, March TH, et al. Histone deacetylase 2 is phosphorylated, ubiquitinated, and degraded by cigarette smoke. Am J Respir Cell Mol Biol, 2009, 40(4): 464-473.
18. Bhavsar P, Ahmad T, Adcock IM. The role of histone deacetylases in asthma and allergic diseases.J Allergy Clin Immunol, 2008, 121(3): 580-584.
19. Ito K, Hanazawa T, Tomita K, et al. Oxidative stress reduces histone deacetylase 2 activity and enhances IL-8 gene expression: role of tyrosine nitration. Biochem Biophys Res Commun, 2004, 315(1): 240-245.
20. Marwick JA, Kirkham PA, Stevenson CS, et al. Cigarette smoke alters chromatin remodeling and induces proinflammatory genes in rat lungs. Am J Respir Cell Mol Biol, 2004, 31(6): 633-642.
21. Guven M, Turan F, Eyibilen A, et al. A comparison of the efficacy of 5-fluorouracil/triamcinolone, carnitine and dexamethasone therapy on wound healing in tracheal injury: potential for preventing tracheal stenosis? Eur Arch Otorhinolaryngol, 2012, 269(1): 201-206.

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Expression of HDAC2 in tracheal granulation tissue and its relationship with tracheal stenosis in animal model of tracheal stenosis

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