HIF-1α在磷酸二酯酶-4抑制剂罗氟司特调节人气道黏蛋白MUCSAC表达中的作用研究

目的探讨缺氧诱导因子-1α（HIF-1α）在磷酸二酯酶4抑制剂罗氟司特调节人气管上皮细胞黏蛋白MUCSAC表达中的作用。方法制备香烟烟雾提取物，分别用罗氟司特或香烟烟雾提取物或二者同时干预支气管上皮细胞16HBE。采用RT—PCR法检测细胞中MUC5AC及HIF-1αmRNA表达量。Western blot检测MUC5AC及HIF-1α蛋白的表达情况。结果与对照组相比，香烟烟雾提取物能够从转录和蛋白水平显著促进支气管上皮细胞16HBE中MUC5AC及HIF-1α的表达，而罗氟司特干预可以明显抑制香烟烟雾提取物诱导的HIF-1α，并降低MUC5AC的表达。结论磷酸二酯酶4抑制剂罗氟司特可以通过降低HIF-1α而抑制香烟烟雾提取物所诱导的支气管上皮细胞MUC5AC的表达。

Role of HIF-let in phosphodiesterase-4 inhibitor roflumilast mediated effect on MUC5AC expression in human bronchial epithelial

Objective To investigate the role of HIF--1α in phosphodiesterase4 inhibitor roflumi-1αst mediated effect on cigarette smoke extract on induced MUC5AC expression in human bronchial epithelial. Methods Cigarette smoke extract was prepared. And human bronchial epithelial cell I6HBE was treated with roflumi-1αst or cigarette smoke extract or both. Then the MUCSAC and HIF-1α mRNA expression were measured by RT-PCR, the protein expression of MUCSAC and HIF-1α were detected by Western blot. Results As compared with the control group, the expression of MUCSAC and HIF--1α were significantly increased after cells treated with cigarette smoke extract at both mRNA and protein level. While,the cigarette smoke extract induced upregu-1αtion of MUC5AC and HIF-1α were inhibited by roflumi-1αst intervention. Conclusions Phosphodiesterase-4 inhibitor roflumi-1αst can reverse the cigarette smoke extract induced MUCSAC upregu-1αtion by inhibiting HIF -1α, expression.