慢性哮喘小鼠肺组织中组蛋白去乙酰化酶8表达和活性增加

Increase in expression and activity of histone deacetylase 8 in the lung tissue of chronic asthmatic mice

目的探讨组蛋白去乙酰化酶8(histone deacetylase 8, HDAC8)在慢性哮喘小鼠肺组织中的表达和活性变化。方法 BALB/C小鼠分为正常组和哮喘组,12只/组。卵蛋白OVA致敏激发方法构建慢性哮喘模型。末次激发试验24h后,收集各组小鼠肺组织标本,免疫组织化学检测HDAC8在肺组织中的表达,Western blot分析HDAC8水平变化,荧光法检测HDAC8酶活性的变化。结果与正常小鼠相比,哮喘小鼠肺组织HDAC8水平和酶活性均显著升高;在正常小鼠肺组织细胞中HDAC8表达极少,哮喘致病时气道上皮细胞、上皮下炎症细胞、血管平滑肌细胞和肺泡腔炎症细胞中HDAC8呈明显阳性表达。结论哮喘致病时肺组织及其中炎性细胞内HDAC8表达表达水平和酶活性增高提示HDAC8可能参与哮喘气道炎症、气道重塑和气道高反应的发生。

Objective To investigate the expression and activity of histone deacetylase 8 （HDAC8） in the lung tissue of chronic asthmatic mice. Methods BALB/C mice were randomly divided into control group and asthma group （n=12 per group）. Ovalbumin sensitization and excitation methods were used to construct chronic asthma model. Lung tissue specimens were collected 24 hours after last ovalbumin stimulation. Then detected the expression localization of HDAC8 in the lung tissue by immunohistochemistry staining, the expression level by western blot and the enzyme activity by fluorescence quantitative method. Results Compared with the control group, the expression level and enzyme activity of HDAC8 were significantly increased in the asthma lung tissue. The HDAC8 was positively expressed in airway epithelial cells, subepithelial inflammatory cells, vascular smooth muscle cells and alveolar inflammato- ry cells during asthma pathogenesis, which was rarely expressed in the normal lung tissue. Conclusion The increase in expression level and enzyme activity of HDAC8 in the lung tissue and its inflammatory cells in asthmatic pathogenesis indicates that HDAC8 might be involved in inflammation, vascular remodeling and hyperreactivity in the airway.