地塞米松对急性过敏性哮喘小鼠肺AQP5表达的影响

目的 观察水通道蛋白5(AQP5)在急性过敏性哮喘小鼠肺组织的改变,以及地塞米松对其的影响,初步探讨AQP5在哮喘发病机制中的作用.方法 建立急性过敏性哮喘小鼠模型,并随机分为急性哮喘组、对照组和地塞米松治疗组,检测支气管肺泡灌洗液(BALF)中自细胞总数及分类计数、ELISA法测定IL-5和IFN-γ水平,RT-PCR和免疫组化法检测AQP5在肺组织的表达以及观察肺组织形态学的改变.结果 (1)哮喘组BALF中白细胞总数、嗜酸性粒细胞数和IL-5水平均高于对照组(P＜0.01),IFN-γ水平低于对照组(P＜0.01),治疗后白细胞总数、嗜酸性粒细胞数和IL-5水平均明显下降(P＜0.05,P＜0.01,P＜0.01),IFN-γ水平明显上升(P＜0.01);(2)哮喘组AQP5 mRNA水平明显高于对照组(P＜0.01),治疗后表达明显下降(P＜0.01);(3)哮喘组肺组织可见较弥漫的炎性改变,黏液分泌增多,血管壁水肿明显,血管周围有大量的炎症细胞渗出物,治疗组形态学改变明显减轻:AQP5表达于正常对照组的肺泡上皮细胞、呼吸道的表层柱状上皮细胞和黏膜下腺腺泡细胞的顶膜,哮喘组表达呈强阳性,地塞米松治疗后表达明显减弱.结论 AQP5在急性哮喘小鼠肺组织内过度表达,可能与黏液高分泌有关,地塞米松可以下调AQP5的表达,可明显减轻小鼠肺部的炎性、水肿和黏液高分泌的病理生理表现.

Effect of dexamethasone on the expression of aquaporin-5 in the lungs of mice with acute allergic asthma

OBJECTIVE: To detect the expression of lung aquaporin 5 (AQP5) in mice with acute allergic asthma and the effect of dexamethasone (DEX) treatment on AQP5 expression, and investigate the role of AOP5 in asthma pathogenesis. METHODS: Mouse models of acute allergic asthma were randomly divided into acute asthma group, normal control group and DEX treatment group. The total number of white blood cells, the subpopulations, and the levels of IL-5 and IFN-gamma were detected in the bronchoalveolar larvage fluid (BALF). The lung tissue AQP5 mRNA expression was detected by RT-PCR, and AQP5 distribution by immunohistochemical method. RESULTS: In asthma group, the total white blood cells, eosinophils and IL-5 levels were all significantly higher (P<0.01) and IFN-gamma levels lower than those of the control group (P<0.01). After DEX treatment, the levels underwent a significant reverse change (P<0.05, P<0.01, P<0.01, and P<0.01, respectively). AQP5 mRNA expression in the asthma group was significantly higher than that in the control group (P<0.01), and was significantly lowered with DEX treatment (P<0.01). Extensive inflammatory changes, mucus hypersecrection, several edema and inflammatory cell infitration around the blood vessels were observed in the lung tissue of the mice in the asthma group. The morphological changes of the treatment group were significantly ameliorated. AQP5 protein was detected in the type I alveolar epithelial cells, the airway columnar epithelial cells and the apical membranes of the submucosal gland acinar cells in the control group. Stronger AQP5 protein expression was found in the asthma group. CONCLUSION: AQP5 is over-expressed in mice with acute asthma which is possibly associated with mucus hypersecrection. DEX can inhibit AQP5 expression and ameliorate allergic airway inflammation, edema and mucus hypersecrection.