Tubastatin A Hcl对慢性支气管哮喘小鼠的治疗作用

发布时间：2018-10-15 08:11

【摘要】：目的探讨组蛋白去乙酰化酶6抑制剂(Tubastatin A Hcl)对慢性支气管哮喘小鼠气道炎症、气道重塑和气道高反应的影响。方法将BALB/C小鼠分为正常组、哮喘组、地塞米松组和Tubastatin A Hcl组。测定气道阻力,计数支气管肺泡灌洗液(BALF)中细胞总数和分类细胞数,ELISA检测白细胞介素(IL)4、IL-5和转化生长因子(TGF)β1。HE、AB-PAS和Masson染色观察气道炎症、气道重塑。免疫组化和Western blotting测定α-平滑肌肌动蛋白(α-SMA)和TGF-β1表达。结果药物治疗后气道阻力降低,BALF中IL-4、IL-5和TGF-β1表达下降,炎症细胞总数和嗜酸性粒细胞数减少;肺组织气道周围炎症减轻,杯状细胞化生降低,胶原沉积减少,且地塞米松治疗效果优于Tubastatin A Hcl。药物治疗后肺组织中α-SMA和TGF-β1表达下降,且Tubastatin A Hcl治疗效果略优于地塞米松。结论 Tubastatin A Hcl能够有效缓解慢性支气管哮喘小鼠气道炎症、气道重塑和气道高反应,其抗炎效果略差于激素,但在抗气道重塑方面略优于激素治疗。
[Abstract]:Objective to investigate the effects of histone deacetylase 6 inhibitor (Tubastatin A Hcl) on airway inflammation, airway remodeling and airway hyperresponsiveness in mice with chronic asthma. Methods BALB/C mice were divided into normal group, asthma group, dexamethasone group and Tubastatin A Hcl group. The airway resistance, the total number of cells and the number of classified cells in bronchoalveolar lavage fluid (BALF) were measured. IL-5 and (TGF) 尾 1. HEAB-PAS and Masson staining were used to detect airway inflammation and airway remodeling by ELISA. The expression of 伪-smooth muscle actin (伪-SMA) and TGF- 尾 1 were detected by immunohistochemistry and Western blotting. Results after drug treatment, the airway resistance decreased, the expression of IL-4,IL-5 and TGF- 尾 1 in BALF decreased, the number of inflammatory cells and eosinophils decreased, the inflammation around the airway decreased, the metaplasia of goblet cells decreased and collagen deposition decreased. The effect of dexamethasone is better than that of Tubastatin A Hcl.. The expression of 伪-SMA and TGF- 尾 1 in lung tissue decreased after drug therapy, and the effect of Tubastatin A Hcl was slightly better than that of dexamethasone. Conclusion Tubastatin A Hcl can effectively relieve airway inflammation, airway remodeling and airway hyperresponsiveness in mice with chronic bronchial asthma. The anti-inflammatory effect of Tubastatin A Hcl is a little worse than that of hormone, but it is slightly superior to hormone therapy in anti-airway remodeling.
【作者单位】：中国医科大学附属第一医院呼吸疾病研究所;
【基金】：国家自然科学基金(81300024) 辽宁省科学技术计划(2013225049) 辽宁省教育厅创新团队(LT2013015)
【分类号】：R562.25

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