Objective To investigate the effects of Tubastatin A Hcl,a selective HDAC6 inhibitor,on the development of chronic asthmatic mice with airway inflammation,airway remodeling and airway hyperresponsiveness. Methods BALB/C mice were randomly divided into control group, asthma group,dexamethasone group and Tubastatin A Hcl group. The airway resistance,total cells and different cells in BALF,IL?4,IL?5,TGF?β1 were detected by ELISA. HE、AB?PAS and Masson trichrome staining were carried out to assess the airway inflammation and remodeling. Immuno?histochemical staining and western blotting were adopted to determine the expression ofα?SMA and TGF?β1. Results After drugs treatment,air?way resistance decreased,and levels of IL?4,IL?5,TGF?β1,total inflammatory cells and eosinophils in BALF were relieved. Meanwhile,inflamma?tory cells infiltration,goblet cells metaplasia and collagen deposition in lung tissue were also reduced,but all of above the effects of dexamethasone were better than Tubastatin A Hcl. The expression ofα?SMA and TGF?β1 in the lung tissue decreased significantly after treatment ,in which Tu?bastatin A Hcl were slightly better than dexamethasone treatment. Conclusion Tubastatin A Hcl can effectively relieve airway inflammation ,air?way remodeling and airway hyperresponsiveness in chronic asthmatic mice ,but its effect of anti?inflammatory is worse than dexamethasone treat?ment,while it is better than dexamethasone in the effect of relief airway remodeling.%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.
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