组蛋白乙酰化修饰在哮喘小鼠气道内黏蛋白5AC表达中的作用研究

目的 探讨哮喘小鼠体内组蛋白乙酰基转移酶（HAT）活性对气道内黏蛋白5AC（MUC5AC）表达的重要性。方法 复制哮喘小鼠模型，行外周血常规分析，肺泡灌洗液常规瑞氏染色并计数，肺组织HE染色，免疫组织化学法检测肺组织内MUC5AC蛋白表达，酶联免疫吸附试验（ELISA）测定HAT、组蛋白去乙酰基酶（HDAC）活性、MUC5AC水平，进行统计学分析。结果 哮喘组小鼠外周血嗜酸性粒细胞计数（EOS）较曲古抑菌素A（TSA）治疗组、对照组均升高（P <0.05）；哮喘组肺泡灌洗液总细胞计数及EOS均较TSA治疗组、对照组升高（P <0.05）；TSA治疗组与哮喘组比较，可同时降低小鼠体内HAT、HDAC活性，差异有统计学意义（P <0.05），但以HAT为主；TSA治疗组MUC5AC水平较哮喘组降低（P <0.05）；肺组织HE染色可见哮喘组小鼠气道炎症细胞增多，而TSA治疗后明显改善；免疫组织化学结果示，TSA治疗组较哮喘组能明显减少MUC5AC蛋白含量（P <0.05）。结论 组蛋白乙酰化修饰在哮喘小鼠气道黏液分泌中起重要的调控作用。

Role of histone acetylation in expression of mucin 5AC in airway of asthmatic mice

Objective To investigate the importance of histone acetyltransferase (HAT) activity on the expression of mucin 5AC (MUC5AC) in the airways of asthmatic mice.Methods A mouse model of asthma was constructed. Peripheral blood was routinely analyzed, alveolar lavage fluid was routinely stained and counted, HE staining was performed in the lung tissue, and MUC5AC protein expression in lung tissue was detected by immunohistochemistry. ELISA was used to determine HAT, histone deacetylase (HDAC) activity, and MUC5AC level. Then statistical analyses were performed.Results Peripheral blood eosinophil count (EOS) in asthma group was higher than that of trichostatin A (TSA) treatment group and control group (P < 0.05). Total cells and EOS of alveolar lavage fluid in asthma group were higher than those of TSA treatment group and control group (P < 0.05). TSA treatment and asthma group can simultaneously reduce the activity of HAT and HDAC in mice (P < 0.05), but mainly HAT. MUC5AC levels in the TSA treatment group were lower than those in the asthma group (P < 0.05). HE staining of lung tissue showed that inflammatory cells in the tract of asthmatic group increased, but significantly improved after TSA treatment. Immunohistochemical results showed that the TSA treatment group can significantly reduce the MUC5AC protein content compared with the asthma group (P < 0.05).Conclusion Histone acetylation plays an important role in the regulation of airway mucus secretion in asthmatic mice.