Effects of Acazolamide on Expression of Aquaporin-1 in Lung Tissues of Asthma Mice_Chinese Journal of Respiratory and Critical Care Medicine

Authors：

TANG Shunguang ¹ , ZHOU Ruixiang ¹ , BEN Suqin ² , NI Songshi. ²

Department of Respiratory Medicine, Gaoyou People’s Hospital. Gaoyou, Jiangsu, 225601, ChinaCorresponding Author: NI Song-shi, E-mail: jsntnss@ 163. com;

Corresponding author：

Keywords：

Acute allergic asthma; Aquaporin-1; Acetazolamide; Interleukin-5; Interferon-γ

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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( P lt;0. 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( P lt;0. 05) , and interferon-γ( IFN-γ) level was lower in group E than in group A ( P lt; 0. 05) . After AZ treatment, the total number of cells, the number of eosinophils, neutrophils and lymphocytes were significantly decreased( P lt; 0. 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( P lt;0. 01) . AQP-1 expression was significantly decreased after the intervention of AZ ( P lt;0. 05) .The decrease was positively correlated with the dose of AZ. The expression of AQP-1 mRNA showed no significant difference among these groups( P gt;0. 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.

Citation： TANG Shunguang,ZHOU Ruixiang,BEN Suqin,NI Songshi.. Effects of Acazolamide on Expression of Aquaporin-1 in Lung Tissues of Asthma Mice. Chinese Journal of Respiratory and Critical Care Medicine, 2010, 9(3): 268-272. doi: Copy

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1. 王吉耀, 主编. 内科学. 北京: 人民卫生出版社, 2006, 159-169.
2. Schwab A. Function and spatial distribution of ion channels and transporters in cell migration. Am J Physiol Renal Physiol, 2001 ,280: F739-F747.
3. 关桂梅, 董震, 吕梅, 等. 鼻息肉组织嗜酸粒细胞中水通道蛋白-1 和抗凋亡基因Bcl-2 mRNA 的表达及意义. 中华耳鼻咽喉头颈外科杂志, 2004 , 8: 476-478 .
4. Saadoun S, Papadopoulos MC, Hara-Chikuma M, et al. Impairment of angiogenesis and cell migration by targeted aquaporin-1 gene disruption. Nature, 2005, 434 : 786-792.
5. Borok Z, Verkman AS. Lung edema clearance: 20 years of progress invited review: role of aquaporin water channels fluid transport in lung and airways. J Appl Physiol, 2002 , 93: 2199-2206.
6. Németh-Cahalan KL, Kalman K, Hall JE.Molecular basis of pH and Ca2 + regulation of aquaporin water permeability. J Gen Physiol,2004, 123: 573-580.
7. Shen HH, Ochkur SI, McGarry MP, et al. A causative relationship exists between eosinophils and the development of allergy pulmonary pathologies in the mouse. J Immunol, 2003, 170: 3296-3305.
8. 沈华浩, 王苹莉. 如何评价哮喘动物模型. 医学与哲学( 临床决策论坛版) , 2007, 2: 13-15.
9. Ferenick M. Handbook of Immunochemistry. London: Chapman & HalI, 1993.
10. Duan W, Aguinaldo Datiles AM, Leung BP, et al. An antiinflammatory role for a phosphoinositide 3 -kinase inhibitor LY294002 in a mouse asthma model. Int Immunopharmacol, 2005 ,5: 495 -502.
11. Takata K, Matsuzaki T, Tajika Y. Aquaporins: water channel Proteins of the cell membrane. Prog Histochem Cytochem, 2004, 39 :1-83.
12. Xiang Y, Ma B, Li T, et al. Acetazolamide inhibits aquaporin-1 protein expression and angiogenesis. Acta Pharmacol Sin, 2004, 25 :812-816.
13. Tanimura Y, Hiroaki Y, Fujiyoshi Y. Acetazolamide reversibly inhibits water conduction byaquaporin-4. J Struct Biol, 2009, 166 :16-21.

Chinese Journal of Respiratory and Critical Care Medicine

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

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