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哮喘小鼠肺组织水通道蛋白5的表达及地塞米松对其的调节
董春玲1,2,鲁继荣2,王桂芳1,李波1,肖奎1,陈智鸿1,白春学1*
0
(1.复旦大学附属中山医院呼吸内科,上海 200032; 2.吉林大学第一医院儿科,长春 130021)
摘要:
目的:探讨支气管哮喘(哮喘)小鼠肺组织中水通道蛋白5(aquaporin 5,AQP5)和黏蛋白5AC(MUC5AC)的变化及地塞米松对其的调节作用。方法:雌性C57BL/6小鼠48只,随机分为对照组、哮喘组和地塞米松干预组,每组16只。测定各组小鼠肺组织病理变化及湿/干质量比值,应用实时定量PCR法测定其肺组织中AQP5和MUC5AC mRNA的表达,应用免疫组化法测定各组AQP5蛋白在肺组织中的分布,免疫印迹法测定AQP5蛋白在肺组织中的表达。ELISA法测定各组支气管肺泡灌洗液中MUC5AC的含量。结果:哮喘组小鼠肺组织中AQP5表达较对照组明显降低\[mRNA减少(42.5±3.6)%,蛋白质减少(64.3±8.2)%\]。而MUC5AC表达显著升高\[mRNA升高(93.3±8.1)%;蛋白质水平升高(98.3±7.2)%\]。地塞米松分别负调节其表达 (与模型组比较P<0.05) 。结论:哮喘小鼠肺组织中AQP5表达明显降低可能与气道MUC5AC表达的升高有关,地塞米松对其显著负调节从而改善气道黏液高分泌、炎性浸润和肺水渗出的病理生理过程。
关键词:  哮喘  水通道蛋白5  黏蛋白类  地塞米松
DOI:10.3724/SP.J.1008.2008.00126
投稿时间:2007-10-19修订日期:2007-11-24
基金项目:国家自然科学基金(30370611); 上海市重点学科建设项目(B115).
Expression of aquaporin 5 in pulmonary tissues of bronchial asthmatic mice and influence of dexamethasone on the expression
DONG Chun-ling1,2,LU Ji-rong2,WANG Gui-fang1,LI Bo1,XIAO Kui1,CHEN Zhi-hong1,BAI Chun-xue1*
(1.Department of Respiratory Medicine,Zhongshan Hospital,Fudan University,Shanghai 200032,China; 2.Department of Pediatrics,The First Affiliated Hospital of Jilin University,Changchun 130021)
Abstract:
Objective:To investigate the expression of aquaporin 5 (AQP5) and MUC5AC in lung of bronchial asthmatic murine model and the regulatory effect of dexamethasone on the expression.Methods: Fortyeight female C57BL/6 mice were evenly randomized into control group,asthma group and dexamethasone group.The pathological changes of the lungs and the wet/dry weight ratios of the lungs were determined in mice of each group.The expression of AQP5 and MUC5AC mRNA in the lung was determined by realtime polymerase chain reaction (realtime PCR); the AQP5 protein was examined by Western blotting assay; the distribution of AQP5 protein in the pulmonary tissue was studied immunohistochemically; and the content of MUC5AC in the bronchial alveolar lavage fluid (BALF) was determined by ELISA.Results: Compared with the control group,the pulmonary expression of AQP5 in asthma group was obviously decreased (mRNA by\[42.5±3.6\]%,protein by \[64.3±8.2\]%),while the expression of MUC5AC was increased (mRNA by\[93.3±8.1\]%,protein by\[98.3%±7.2\]%) .Dexamethasone significantly decreased the pulmonary expression of AQP5 and MUC5AC compared with the asthma group (P<0.05).Conclusion: The decreased pulmonary expression of AQP5 in asthmatic mice might be related to the elevation of MUC5AC expression in the airway; dexamethasone can decrease AQP5 expression and therefore alleviate the overproduction of airway mucus,pulmonary inflammation and lung edema.
Key words:  asthma  aquaporin 5  mucins  dexamethasone