MAPK／Foxa2参与吸烟大鼠模型支气管上皮细胞的异常分化  

MAPK/Foxa2 involved in abnormal differentiation of bronchial epithelial cells in cigarette smoking rat model

作　　者：杜春玲[1] 段艳红[1] 周磊[1] 吴波[1] 

机构地区：[1]复旦大学附属中山医院青浦分院呼吸内科,上海201700

出　　处：《临床内科杂志》2015年第7期483-486,共4页Journal of Clinical Internal Medicine

基　　金：上海市卫计委资助项目（20120277）

摘　　要：目的采用大鼠吸烟模型，探讨吸烟对丝裂原活化蛋白激酶（MAPK）信号通路、叉头框蛋白a2（Foxa2）及支气管上皮细胞分化的影响。方法将40只大鼠随机分为5组（n=8）：空白对照组、吸烟组、吸烟＋U0126（ERK抑制剂）组、吸烟＋SB203580（p38抑制剂）组、吸烟＋SP600125（JNK抑制剂）组。连续吸烟造模并同时给药干预90天后，采用酶联免疫吸附试验（ELISA）法检测各组磷酸化ERKI／2、JNK、p38蛋白水平，采用实时荧光定量聚合酶链反应（Real—timePCR）检测Foxa2、E-钙黏索（E—cadherin）的mRNA水平；采用Westernblot检测Foxa2、E—cadherin蛋白水平；用组织切片染色法观察支气管上皮细胞形态学变化。结果与对照组比较，吸烟组大鼠支气管、肺组织磷酸化ERK、038以及JNK蛋白表达升高（P〈0．05），Foxa2及E—cadherinmRNA及蛋白水平明显下降（P〈0．05），支气管上皮增生，局部有鳞状化生。ERK、p38以及JNK的特异性抑制剂均能明显改善Foxa2、E—cadherin的变化（P〈0．05）以及气道的鳞状化生。结论吸烟会导致气道上皮细胞的异常分化，MAPK／Foxa2通路参与介导了吸烟所导致的支气管上皮细胞的异常分化。Objective Toexplore the effects of cigarette smoking（CS）exposure on mitogen-aetivated protein kinase （MAPK） signaling pathways, Foxa2 and the differentiation of the bronchial epithelial cell in CS rat model. Methods 40 rats were randomly divided into 5 groups, control group, CS group, CS ＋ U0126 group, CS ＋ SB203580 group, CS ＋ SP600125 group. Sprague-Dawley rats were used to challenge with CS exposure for 90 days. At the same time, MAPK inhibitors were administrated for 90 days, the phos- phorylations of ERK, p38 and JNK were measured by ELISA. The mRNA and protein expression of Foxa2 and E-cadherin were measured by quantitative real-time polymerase chain reaction （PCR） and Western blotting,respectively. Histological staining to observe the morphological changes of t bronchial epithelial cells. Results In CS group,the phosphorylations of ERK,p38 and JNK protein expression in lung tissue were significantly increased when compared with control group, meanwhile mRNA and protein levels of Foxa2 and E-adhefin were significantly decreased, bronchial epithelial hyperplasia and local squamous metaplasia were observed. While in MAPK inhibitors group, included in the ERK, p38 and JNK inhibitors, the expression of Foxa2 and E-cadherin were significantly improved, and squamous metaplasia of the epithelial cells also were decreased. Conclusion Cigarette smoking can lead to abnormal airway epithelial cell differentiation,involved in MAPK/Foxa2 pathways.

关 键 词：MAPK Foxa2 吸烟 支气管上皮细胞 异常分化 

分 类 号：R734.2[医药卫生—肿瘤]