Therapeutic effects of Tubastatin A Hcl on airway inflammation in acute mice asthma model

Abstract

Objective: To investigated the therapeutic effects of Tubastatin A Hcl, a selective HDAC6 inhibitor, on airway inflammation in acute mice bronchial asthma (asthma) model. Methods: 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. Results: 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), P<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 P<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 P>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 P<0.05). Although collagen deposition in the lung tissue of Tubastatin A Hcl group was lower than asthma group, there were no significant differences (P>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 (P>0.05). Conclusion: 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.