中文摘要：

目的探讨蛙皮素受体激活蛋白（BRAP）对脂多糖（LPS）诱导的气道黏液高分泌的影响及相关作用机制。方法体外培养人气道上皮HBE16细胞,转染已构建好的p EGFP-N1-BRAP,以空质粒载体作为对照,给予LPS刺激,同时分别以ERK抑制剂U0126、JNK抑制剂SP600125、P38抑制剂SB203580干预。观察细胞内活性氧（ROS）含量、黏蛋白（MUC）5AC表达和核因子-κB（NF-κB）活性以及细胞活力的变化。结果转染p EGFP-N1-BRAP后ROS明显减少（P〈0.01）;同单纯LPS刺激相比,MUC5AC蛋白含量和mRNA水平在转染p EGFP-N1-BRAP后明显降低（P〈0.01）,NF-κB活性亦呈相同趋势（P〈0.05）;在U0126组,MUC5AC的表达较转染重组质粒组显著降低（P〈0.01）,NF-κB活性也显著下调（P〈0.05）。结论 BRAP可以通过ROS/ERK/MAPK信号通路阻止胞质内NF-κB的活化,从而下调MUC5AC的生成。

英文摘要：

Objective To investigate the effect of bombesin receptor activated protein（ BRAP） on lipopolysaccharide（ LPS）-induced mucous hypersecretion in airway and mechamism. Methods After cultivating HBE16 cells in vitro,the constructed p-EGFP-N1-BRAP eukaryotic vector was transfected into the cells with empty plasmid as a vector control. At the same time in order to LPS as a stimulus to extracellular signal-regulated protein kinase（ ERK） specific inhibitor U0126,P38 inhibitor SB203580 and c-jun N-terminal kinase（ JNK） inhibitor SP600125 for the intervention factors. The content of ROS,the expression of MUC5 AC mRNA and protein,the NF-κB activity and cell vitality were detected. Results After transfected p EGFP-N1-BRAP,ROS production was decreased（ P〈0. 01）. The MUC5 AC protein production and mRNA level of the group transfected p EGFPN1-BRAP were significantly decreased as compared with LPS group（ P〈0. 01）,the NF-κB activity showed the same trend（ P〈0. 05）. In U0126 group,the expression of MUC5 AC was significantly decreased as compared with transfected recombination plasmid group（ P〈0. 01）,the NF-κB activity was also significantly decreased（ P〈0. 05）. Conclusions BRAP inhibits NF-κB activation via ROS /ERK/MAPK signaling pathway,thus reducing LPS-induced MUC5 AC production.