克拉霉素抑制气道黏液高分泌细胞内机制的研究  

Clarithromycin inhibits airway mucous hypersecretion intracellular mechanism

作　　者：罗琳[1] 尤列.皮尔曼 维克多.科罗索夫 周向东[1] 

机构地区：[1]重庆医科大学附属第二医院,重庆400010 [2]俄罗斯医学科学院远东呼吸生理与病理中心,布拉戈维申斯克675000

出　　处：《中国抗生素杂志》2011年第8期630-634,共5页Chinese Journal of Antibiotics

基　　金：国家自然科学基金(81070031);国家自然科学基金中俄国际合作项目(81011120108);中俄政府间合作项目(2009:13-01)

摘　　要：目的研究克拉霉素(CLA)抑制气道黏液高分泌的细胞内分子机制。方法运用中性粒细胞弹性蛋白酶(NE)刺激人类支气管上皮细胞株HBE16构建气道黏液高分泌模型,予以CLA和信号末端调节激酶1/2(ERK1/2)特异性抑制剂U0126进行干预,采用RT-PCR检测细胞内黏蛋白(MUC)5AC mRNA表达水平,ELISA法检测细胞上清液中MUC5AC蛋白含量,Western blotting检测细胞内磷酸化表皮生长因子受体(p-EGFR)、磷酸化ERK(p-ERK)、磷酸化c-Jun N端激酶(p-JNK)、磷酸化P38(p-P38)的含量。结果克拉霉素和U0126均能降低气道黏液高分泌模型中MUC5AC基因转录和蛋白表达水平,并且使p-ERK表达水平下降,但对p-EGFR、p-JNK、p-P38的表达无明显作用。结论克拉霉素能抑制细胞内信号通路分子ERK1/2磷酸化水平,从而减少了气道上皮细胞产生MUC5AC,由此发挥抑制气道黏液高分泌的作用。Objective To investigate the inhibit effect of clarithromycin （CLA） on airway mucous hypersecretion and it＇s intracellular molecule mechanism. Methods Stimulated human bronchial epithelial cell line HBE16 with neutrophil elastase （NE） to create airway mucous hypersecretion model, interfered the model with CLA and external-signal regulated kinase 1/2 （ERK1/2） specific inhibitor U0126 respectively. Gene transcription and protein expression levels of mucin（MUC）5AC in each group were analyzed by quantitative RT-PCR and ELISA. Phosphorylated epidermal growth factor receptor （p-EGFR）, Phosphorylated ERK （p-ERK）, Phosphorylated c-jun N-terminal kinase （p-JNK） and Phosphorylated P38 （p-P38） were all analyzed by Western blotting. Results CLA and U0126 reduced the the levels of MUC5AC gene transcription and protein expression in airway mucous hypersecretion model, also the protein expressions of p-ERK. But CLA and U0126 didn＇t reduce the expressions of p-EGFR, p-JNK and p-P38 obviously. Conclusion CLA could inhibit the intracellular signaling pathway molecule ERK1/2＇s phosphorylation level thereby reduce the production of MUC5AC in airway epithelial cells, thus might inhibits airway mucous hypersecretion.

关 键 词：黏蛋白5AC 中性粒细胞弹性蛋白酶 克拉霉素 信号末端调节激酶 

分 类 号：R978.15[医药卫生—药品]