TubastatinAHcl对急性支气管哮喘小鼠气管炎症的干预作用

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

目的探讨组蛋白脱乙酰基酶6（HDAC6）抑制剂Tubastatin A Hcl对急性支气管哮喘（简称哮喘）小鼠气管炎症的干预作用。方法48只BALB／C小鼠按随机数字表法随机分为正常组、哮喘组、地塞米松组和Tubastatin A Hcl组各12只。测定各组小鼠气管反应性，计数其支气管肺泡灌洗液（BALF）中细胞总数和分类细胞数以及白细胞介素（IL）-4、IL-5和γ干扰素（IFN-γ）水平。取各组小鼠肺组织分别通过HE染色观察气管炎症浸润、AB-PAS染色观察气管上皮杯状细胞化生、Masson染色观察肺组织胶原沉积情况。结果Tubastatin A Hcl组气管反应性显著低于哮喘组[（4．18±0．94）比（6．02±0．47），P〈0．05]；Tubastatin A Hcl组BALF中炎症细胞总数[（57．0±5．7）×10^4／ml比（87．0±5．6）×10^4／m1]、嗜酸性粒细胞数[（6．8±1．7）×10^4／ml比（12．3±3．5）×10^4／m1]、IL-4[（19．3±2．7）比（26．2±3．2）ng／ml]水平均显著低于哮喘组（均P〈0．05），IL-5低于哮喘组、IFN-γ水平高于哮喘组但差异均无统计学意义（均P〉0．05）；Tubastatin A Hcl组肺组织气管血管周围炎症细胞浸润程度、炎症细胞数[（9．80±2．42）比（20．67±7．53）个]、炎症评分[（2．20±0．70）比（3．60±0．68）分]、杯状细胞化生百分比[（50．46±5．03）％比（71．06±5．38）％]均显著低于哮喘组（均P〈0．05），胶原沉积面积低于哮喘组但差异无统计学意义（P〉0．05）。但上述结果地塞米松组均略优于TubastatinAHcl组但差异均无统计学意义（均P〉0．05）。结论Tubastatin A Hcl能够有效缓解急性期哮喘气管炎症水平，但其抗炎作用有限，效果并不如地塞米松显著。

Objective To investigated the therapeutic effects of Tubastatin A Hel, 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 ceils 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/roll, eosinophil cells [ （6. 8 ± 1.7）×10^4/mlvs （12.3 ±3.5）×10^4/mll 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.