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

Expression of aquaporin 5 in pulmonary tissues of bronchial asthmatic mice and influence of dexamethasone on the expression

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。

Objective：To investigate the expression of aquaporin 5 （AQPS） and MUCSAC 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 MUCSAC 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 MUCSAC 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±8.21%） ,while the expression of MUCSAC was increased （mRNA by[93.3±8. 1]% ,protein by[98.3% ±7.21%） . Dexamethasone significantly decreased the pulmonary expression of AQP5 and MUCSAC 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 MUCSAC expression in the airway; dexamethasone can decrease AQP5 expression and therefore alleviate the overproduction of airway mucus, pulmonary inflammation and lung edema.