哮喘气道重塑大鼠中磷酸化p38丝裂原活化蛋白激酶的表达对黏液细胞增殖的影响及布地奈德的干预作用

中国临床药理学与治疗学 ›› 2009, Vol. 14 ›› Issue (8): 866-871.

哮喘气道重塑大鼠中磷酸化p38丝裂原活化蛋白激酶的表达对黏液细胞增殖的影响及布地奈德的干预作用

郑仰明, 李昌崇, 张维溪, 管小俊

温州医学院附属育英儿童医院呼吸科, 温州 325027, 浙江

收稿日期:2009-04-16 修回日期:2009-06-11 出版日期:2009-08-26 发布日期:2020-10-30
通讯作者: 李昌崇,男, 博士生导师, 主任医师。Tel:13806559566 E-mail:wzlichch@21cn.com
作者简介:郑仰明, 男, 硕士, 医师, 研究方向:儿科呼吸。Tel:13605775149 E-mail:zym002@126.com
基金资助:
国家科学自然基金资助项目(30271383)

Expression of phospho-p38MAPK in asthmatic rats with airway remodeling the effect on proliferation of mucous cells and the regulation of budesonide

ZHENG Yang-ming, LI Chang-chong, Zhang Wei-xi, GUAN Xiao-jun

Department of Respiratory Medicine, Yuying Children's Hospital Affiliated to Wenzhou Medical College, Wenzhou 325027, Zhejiang, China

Received:2009-04-16 Revised:2009-06-11 Online:2009-08-26 Published:2020-10-30

摘要/Abstract

摘要： 目的: 观察磷酸化 p38 丝裂原活化蛋白激酶在哮喘气道重塑大鼠肺组织的表达及对其黏液细胞增殖的作用及布地奈德对哮喘气道重塑大鼠肺组织中磷酸化 p38 丝裂原活化蛋白激酶的表达和黏液细胞增殖的干预作用。方法: 30只雄性 SD大鼠随机分为对照组(C 组) 、哮喘气道重塑组(A组) 、布地奈德治疗组(B 组) 。建立哮喘气道重塑模型, 肺组织用于 Masson 三色染色、过碘酸-雪夫氏染色, 免疫组化染色, 光镜电镜观察。结果: 光镜及电镜均发现 A 组明显的气道重塑病理改变,B 组较A 组有所减轻;图像分析结果 :支气管壁厚度及平滑肌厚度比较, A 组均明显高于 C 组, B 组明显低于A 组, 但仍高于 C 组。气道黏液细胞百分比比较,A 组明显高于 C 组 (P<0.01) , B 组明显低于 A 组(P<0.05) , 但 B 组仍高于 C 组(P<0.01) 。各组大鼠气道上皮磷酸化 p38MAPK 表达的比较, A 组明显高于 C 组 (P<0.01);B 组明显低于A 组(P<0.05) 。磷酸化 p38MAPK 表达水平与黏液细胞百分比呈显著正相关(n =30, r =0.813, P<0.01) 。结论: 气道上皮磷酸化p38MAPK 表达增加可能促使哮喘气道重塑大鼠黏液细胞增殖;布地奈德能抑制哮喘气道重塑大鼠中磷酸化 p38MAPK 的表达从而抑制黏液细胞增殖。

关键词: 哮喘, 大鼠, 气道重塑, 黏液细胞, 布地奈德

Abstract: AIM: To investigate the protein ex-pression of phospho-p38MAPK in asthmatic rats with airway remodeling and its effects on proliferation of mu-cous cells and the regulation role of budesonide. METHODS: Thirty male rats were randomly divided into control group (Group C, n =10) , airway remodeling group(Group A, n=10) and budesonide treated group (Group B, n =10) .The asthmatic rat model with airway remodeling was established. The lung tis-sue was observed by Hematoxylin and eosin staining, Masson' s Trichrome stain, Periodic Acide Schiff' and immunohistochemistry staining .RESULTS: Pathological changes of airway remodeling were found under light microscope and TEM .Compared with Group A, the pathologic change in group B was relieved. The results of image analysis: compared with Group A, the total bronchial wall area(Wat) and the smooth muscle area (Wam) and the percentage of mucous cells in rat air-way epithelium were significantly decreased in Group C and Group B, but the Wat and Wam in group B were higher than those in Group C. Compared with Group A, the contents of phospho-p38MAPK protein in group B and group C were decreased .There were significant positive correlation between the contents of phospho-p38MAPK and percentage of mucous cells(n =30, r = 0.813, P<0.01) .CONCLUSION: High expression of phospho-p38MAPK might precipitate the proliferation of mucous cells in asthmatic rats. Budesonide can inhibit the expression of phospho-p38MAPK protein in the airway epithelium of asthmatic rats with airway re-modeling, by which might inhibit proliferation of mucous cells.

Key words: asthma, rat, airway remodeling, mucous cell, budesonide

中图分类号:

R965.2

郑仰明, 李昌崇, 张维溪, 管小俊. 哮喘气道重塑大鼠中磷酸化p38丝裂原活化蛋白激酶的表达对黏液细胞增殖的影响及布地奈德的干预作用[J]. 中国临床药理学与治疗学, 2009, 14(8): 866-871.

ZHENG Yang-ming, LI Chang-chong, Zhang Wei-xi, GUAN Xiao-jun. Expression of phospho-p38MAPK in asthmatic rats with airway remodeling the effect on proliferation of mucous cells and the regulation of budesonide[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2009, 14(8): 866-871.

参考文献

[1] Holgate ST, Davies DE, Puddicombe S, et al.Mecha-nisms of airway epithelial damage:epithelial-mesenchymal interactions in the pathogenesis of asthma[J] .Eur Respir J Suppl, 2003, 44:24-29.
[2] Newton R, Holden N, et al.Inhibitorsof p38mitogen-ac-tivated protein kinase:potential as anti -inflammatory agentsin asthma[J] ? Bio Drugs, 2003, 17(2):113-129.
[3] Palmans E, Kips JC, et al.Pauwels RA.Prolonged aller-gen exposure induces structural airway changes in sensi-tized rats[J] .Am J Respir Crit Care Med, 2000, 161(2): 627-635.
[4] Bai A, Eidelman DH, Hogg JC, et al.Proposed nomen-clature for quantifying subdivisions of the bronchial wall[J] .J Appl Physiol, 1994, 77(2):1011-1014.
[5] Fujisswa T, Ide K, Holtzman MJ, et al.Involvement of the p38MAPK pathway in IL-13-induced mucous cell metaplasia in mouse tracheal epithelial cells[J] .Respirol-ogy, 2008, 13(2):191-202.
[6] Wei Duan, Jasmine H.P.Chan, Kelly Mckay, et al. In-haled p38 Mitogen-activated Protein Kinase Antisense Oli-gonucleotide AttenuatesAsthma inMice[J] .Am J Respir Crit Care Med, 2005, 171:571-578.
[7] Pelaia G, Cuda G, Vatrella A, et al.Effectsof glucocor-ticoids on activation of c-JunN-terminal, extracellular sig-nal -regulated, and p38 MAP kinases in human pulmonary endothelialcells[J] .Biochem Pharmacol, 2001, 62(12): 1719-1724.
[8] Hashimoto S, GonY, Matsumoto K, et al. Inhalant corti-costeroids inhibit hyperosmolarity-induced, and cooling and rewarming-induced interleukin-8 and RANTES pro-duction by human bronchial epithelial cells[J] .Am J Re-spir Crit Care Med, 2000, 162(3):1075-1080.
[9] Chetta A, Zanini A, ForesiA, et al. Vascular component of airway remodeling in asthma is reduced by high dose of fluticasone[J] .Am J Respir Crit Care Med, 2003, 167(5):751-757.
[10] Kawaguchi M, Kokubu F, Matsukura S, et al.Induction of C-X-C chemokines, growth-related oncogene alpha ex-pression, and epithelial cell-derived neutrophil -activating protein-78 by ML-1 (interleukin-17F) involves activation of Raf1-mitogen-activated protein kinase kinase-extracellu-lar signal-regulated kinase 1 2 pathway[J] .J Pharmacol Exp Ther, 2003, 307(3):1213-1220.
[11] 罗丽丹, 金小红, 董夏生, 等.生长相关癌基因α在大鼠哮喘中的表达意义及地塞米松对其的影响[J] .中国临床药理学和治疗学, 2008, 13(4):396-400.
[12] 管小俊, 张维溪, 李昌崇, 等.细胞外信号调节激酶和转化生长因子在哮喘气道重塑中的作用以及糖皮质激素的调控[J] .中华医学杂志, 2007, 87(25):1767-1772.

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