罗氟司特抑制吸烟诱导的慢性阻塞性肺疾病大鼠气道黏液高分泌的分子机制研究  

The Molecular Mechanism of Roflumilast on Mucus Hypersecretion in Cigarette Smoking-induced COPD Rat Airway

作　　者：董玉[1] 李满祥[2] 刘志燕[1] 

机构地区：[1]西安市中心医院呼吸内科 [2]西安交通大学医学院第二附属医院呼吸内科,陕西西安710003

出　　处：《昆明医科大学学报》2014年第4期21-24,29,共5页Journal of Kunming Medical University

基　　金：陕西省科学技术研究发展计划基金资助项目(2012K16-01-06)

摘　　要：目的探讨磷酸二酯酶4抑制剂罗氟司特对慢性阻塞性肺疾病(COPD)大鼠肺组织MUC5AC表达的影响及其分子机制.方法 Wistar大鼠随机分为对照组、烟雾组、罗氟司特组、烟雾+罗氟司特组.对照组和罗氟司特组大鼠置于无烟环境中饲养,烟雾组和烟雾+罗氟司特组大鼠暴露于有烟环境,免疫组化法检测各组大鼠肺组织MUC5AC、p-ERK1/2及p-JNK1/2的表达,Western Blot检测MUC5AC、ERK1/2、p-ERK1/2、JNK1/2p-JNK1/2蛋白的表达情况.结果与对照组相比,烟雾组大鼠肺组织MUC5AC的阳性率显著升高.且相关通路分子ERK1/2及JNK1/2的磷酸化水平明显升高.而烟雾+罗氟司特组MUC5AC的表达水平较烟雾组显著降低,其ERK1/2及JNK1/2的磷酸化水平低于烟雾组.结论磷酸二酯酶4抑制剂罗氟司特可能通过抑制ERK、JNK等通路活化而减少吸烟鼠肺组织MUC5AC的表达,改善COPD.Objective To investigate the effect of phosphodiesterase-4 inhibitor roflumilast on airway mucus hypersecretion in rats and its molecular mechanism. Methods Wistar rats were randomly divided into control group, smoking group, roflumilast group, smoking ＋ roflumilast group. Control group and roflumilast group rats were placed in smoke-free environment, while, rats in smoking group and smoking ＋ roflumilast group are exposed to smoke environment. Immunohistochemical method was used to detect the expression of MUC5AC, p-ERK1/2 and p-JNK1/2 in lung tissue of each group. The protein expression of MUC5AC and related pathways molecular （ERK1/2, P-ERK1/2, JNK1/2, P- JNK1/2） were measured Western Blot. Results The protein expression levels of MUC5AC were significantly increased in lung tissue of smoking group as compared with the normal control group, accompanying with the increased phosphorylation level of ERK1/2, JNK1/2. The expression level of MUC5AC in smoking ＋ roflumilast group was reduced significantly as compared with the smoking group, and the ERK1/2, JNK1/2 pathway activity was also inhibited. reverse the smoking induced MUC5AC expression in JNK1/2 pathway. Conclusion Phosphodiesterase-4 inhibitor roflumilast can rat lung tissue and improve COPD via inhibiting ERK1/2,

关 键 词：罗氟司特 慢性阻塞性肺疾病 气道黏液高分泌 MUC5AC 

分 类 号：R563.3[医药卫生—呼吸系统]