p38MAPK与MMP-9在气道粘液高分泌中的调控作用  

Effect of p38 MAPK and MMP-9 signaling pathway on airway mucus hypersecretion

作　　者：刘代顺[1] 文富强[2] 陈亚娟[2] 

机构地区：[1]贵州省遵义医院呼吸内科,贵州遵义563002 [2]四川大学华西医院呼吸内科,四川成都610041

出　　处：《西部医学》2007年第3期335-338,共4页Medical Journal of West China

基　　金：国家杰出青年科学基金(30425007);美国纽约CMB基金(00-722)

摘　　要：目的了解基质金属蛋白酶9(MMP-9)与p38丝裂原激活蛋白激酶(p38M APK)在气道粘液高分泌中的调控作用。方法利用小鼠吸入丙烯醛(21天)构建气道粘液高分泌模型,对照组采用生理盐水吸入,干预组予p38MAPK特异性抑制剂SB 203580腹腔注射。应用A日-PA S、1mmU nO h istO chem ist叮、RT-PCR和W estefri-b,ot等方法,于第7天、第21天时间点取标本检测。结果丙烯醛可致小鼠出现明显的气道粘液高分泌表现,拮抗p38M APK后气道粘液物质减少、MUC 5AC和MMP-9蛋白、mRNA表达量下降。结论p38M APK信号通路特异抑制剂可减轻气道粘液分泌,其机制可能涉及调控MMP-9,从而下调MUC 5AC表达。Objective To study the effect of p38 mitogen-activated protein kinases （MAPK） and matrix metalloproteinases （MMP）-9 signaling pathway on airway mucus hyperseeretion. Methods Mice were inhaled aerolein for 21 days to set up the model of airway mucus hyperseeretion. At the same time, mice exposed aerolein were given S8203580, a p38 MAPK special inhibitor intraperitoneally during the entire experimental time, while mice in control group were received normal saline only. Animals were killed in order to reveal airway mucus overproduction by the methods of AB-PAS, immunohistoehemistry, RT-PCR and Western-blot on days 7 and 21. Results Aerolein resulted in a notable a way mucus overproduction and in turn mueosubstanee. MUCSAC, MMP-9 protein and mRNAwas decreased after SB203580 administration. Conclusion This study suggests that mucus overproduction in murine airway induced by aerolein can be ameliorated via blocking p38 MAPK signaling pathway, in which controlling the activation of MMP-9 gene may contribute to the main mechanism of MUCSAC down-regulation.

关 键 词：气道粘液高分泌 MMP-9 P38丝裂原激活蛋白激酶 

分 类 号：R563.19[医药卫生—呼吸系统]