急性哮喘小鼠肺组织水通道蛋白1的表达变化及乙酰唑胺对其表达的影响

Effects of Acazolamide on Expression of Aquaporin-1 in Lung Tissues of Asthma Mice

目的观察水通道蛋白1(AQP-1)在急性过敏性哮喘小鼠肺组织表达的变化,以及乙酰唑胺(AZ)对AQP-1表达的影响。方法 40只C57BL/6小鼠随机分对照组(A组)、AZ大剂量干预组(300mg/kg,B组)、AZ中剂量干预组(200mg/kg,C组)、AZ小剂量干预组(100mg/kg,D组)和哮喘组(E组),每组8只。干预组在激发阶段给予不同剂量的AZ腹腔注射。结果①E组肺组织的湿干重比值比A组明显增高(P<0.05);B、C、D组肺组织的湿干重比值较E组显著减低(P<0.05),与剂量呈负相关性。②E组BALF中细胞总数、嗜酸粒细胞数和IL-5水平均高于A组(P<0.05),IFN-γ水平低于A组(P<0.05),治疗后细胞总数、嗜酸粒细胞数、中性粒细胞及淋巴细胞均明显下降(P<0.05),且与剂量呈正相关性。③E组AQP-1在气管黏膜上皮、微血管内膜上皮、支气管周围血管床及炎症细胞呈强阳性表达,其表达水平明显高于A组(P<0.01),使用AZ干预后表达明显低于E组(P<0.05),下降的幅度与剂量呈正相关性;但AQP-1mRNA检测结果无明显差异(P>0.05)。结论①AQP-1在急性哮喘小鼠肺组织内及炎症细胞上过度表达,E组呈强阳性表达。②AZ对AQP-1有显著的抑制作用,可明显改善小鼠肺部的炎性细胞浸润等病理改变,且呈剂量依赖性。③AQP-1蛋白质在各组中表达差异较大,但AQP-1mRNA无明显差异,提示乙酰唑胺对AQP-1的影响可能是在转录后的水平上。

Objective To investigate the expression of aquaporin-1（AQP-1） in pulmonary tissues of asthma mice and the effects of acetazolamide（AZ） on AQP-1 expression.Methods Forty C57BL/6 mice were randomly divided into five groups.Group A was treated with phosphate buffer as a non-asthmatic group.The mice in group B,C,D,and E were sensitized with ovalbumin（OVA） and challenged with aerosol OVA to establish asthma model.The mice in group B,C,and D were interperitoneally injected with AZ at doses of 300,200,100 mg/kg,respectively during the challenge period.Results ①Wet/dry weight ratio of lung tissues in group E was significantly higher than that in group A（P0.05）,while it was lower in B,C and D groups than group E.②The total number of cells,the number of eosinophils,and interleukin-5（IL-5） in BALF of group E were higher than those in group A（P0.05）,and interferon-γ（IFN-γ） level was lower in group E than in group A（P0.05）.After AZ treatment,the total number of cells,the number of eosinophils,neutrophils and lymphocytes were significantly decreased（P0.05）,which were positively correlated with the dose of AZ.③AQP-1 were expressed in tracheal epithelium,microvascular endothelial cell and bronchial peripheral vascular bed,and the expression in group E was significantly higher than that in group A（P0.01）.AQP-1 expression was significantly decreased after the intervention of AZ （P0.05）.The decrease was positively correlated with the dose of AZ.The expression of AQP-1 mRNA showed no significant difference among these groups（P0.05）.Conclusions AQP-1 was over-expressed in the lung tissue of mice with asthma.AZ can inhibit the expression of AQP-1 and relieve lung inflammatory cells infiltrationin a dose-dependent manner.It is the protein expression of AQP-1 not the AQP-1 mRNA which were significantly different in different groups,suggesting that AZ affected AQP-1 in the post-transcriptional stage.