Su X M, Ren Y, Li M L, Zhao X, Kang J
Institute of Respiratory Disease, the First Affiliated Hospital of China Medical University, Shenyang 110001, China.
Zhonghua Yi Xue Za Zhi. 2017 Jun 27;97(24):1888-1892. doi: 10.3760/cma.j.issn.0376-2491.2017.24.010.
To investigated the therapeutic effects of Tubastatin A Hcl, a selective HDAC6 inhibitor, on airway inflammation in acute mice bronchial asthma (asthma) model. A total of 48 BALB/C mice were randomly divided into control group, asthma group, dexamethasone group and Tubastatin A Hcl group with 12 mice in each group. Then the airway hyperresponsiveness was assessed in each group; total cell number, different cell number, levels of Interleukin (IL)-4, IL-5 and Interferon-γ (IFN-γ) in the bronchoalveolar lavage fluid (BALF) were detected; the lung tissues of each group were stained with HE to observe the inflammatory cells infiltration. AB-PAS was used to observe the goblet cell metaplasia in tracheal epithelium. Masson staining was used to observe the collagen deposition in lung tissue. The airway reactivity in Tubastatin A Hcl group was significantly lower than that in asthma group [(4.18±0.94) vs (6.02±0.47), <0.05]; in the Tubastatin A Hcl group, the total inflammatory cells [(57.0±5.7)×10(4)/ml vs (87.0±5.6)×10(4)/ml], eosinophil cells [(6.8±1.7)×10(4)/ml vs (12.3±3.5)×10(4)/ml] and levels of IL-4 [(19.3±2.7) vs (26.2±3.2)ng/ml] in BALF were obviously lower than those of asthma group (all <0.05); IL-5 in Tubastatin A Hcl group was lower and IFN-γ was higher than that of asthma group, while there were no significant differences (both >0.05). The degree of inflammatory cells infiltrations around the airway and vascular, number of inflammatory cells [(9.80±2.42) vs (20.67±7.53)], score of inflammation [(2.20±0.70) vs (3.60±0.68) points, ], and percentage of goblet cell metaplasia [(50.46±5.03)% vs (71.06±5.38)%] in the lung tissue of Tubastatin A Hcl group were lower than that of asthma group (all <0.05). Although collagen deposition in the lung tissue of Tubastatin A Hcl group was lower than asthma group, there were no significant differences (>0.05). However, all of the above results in the dexamethasone group were slightly better than Tubastatin A Hcl group, which had no significant differences (>0.05). Tubastatin A Hcl can effectively alleviate the level of airway inflammation in acute asthma, but its anti-inflammatory effect is limited, which is not as significant as dexamethasone.
为研究选择性HDAC6抑制剂盐酸图巴他汀A对急性小鼠支气管哮喘模型气道炎症的治疗作用。将48只BALB/C小鼠随机分为对照组、哮喘组、地塞米松组和盐酸图巴他汀A组,每组12只。然后评估每组的气道高反应性;检测支气管肺泡灌洗液(BALF)中的总细胞数、不同细胞数、白细胞介素(IL)-4、IL-5和干扰素-γ(IFN-γ)水平;对每组肺组织进行HE染色以观察炎症细胞浸润。采用AB-PAS法观察气管上皮杯状细胞化生。采用Masson染色法观察肺组织中的胶原沉积。盐酸图巴他汀A组的气道反应性显著低于哮喘组[(4.18±0.94)对(6.02±0.47),<0.05];在盐酸图巴他汀A组中,BALF中的总炎症细胞[(57.0±5.7)×10⁴/ml对(87.0±5.6)×10⁴/ml]、嗜酸性粒细胞[(6.8±1.7)×10⁴/ml对(12.3±3.5)×10⁴/ml]和IL-4水平[(19.3±2.7)对(26.2±3.2)ng/ml]明显低于哮喘组(均<0.05);盐酸图巴他汀A组的IL-5较低,IFN-γ高于哮喘组,但差异无统计学意义(均>0.05)。盐酸图巴他汀A组气道和血管周围的炎症细胞浸润程度、炎症细胞数量[(9.80±2.42)对(20.67±7.53)]、炎症评分[(2.20±0.70)对(3.60±0.68)分]以及肺组织中杯状细胞化生百分比[(50.46±5.03)%对(71.06±5.38)%]均低于哮喘组(均<0.05)。虽然盐酸图巴他汀A组肺组织中的胶原沉积低于哮喘组,但差异无统计学意义(>0.05)。然而,地塞米松组的上述所有结果均略优于盐酸图巴他汀A组,差异无统计学意义(>0.05)。盐酸图巴他汀A可有效减轻急性哮喘的气道炎症水平,但其抗炎作用有限,不如地塞米松显著。