目的 觀察水通道蛋白1( AQP-1) 在急性過(guò)敏性哮喘小鼠肺組織表達(dá)的變化, 以及乙酰唑胺( AZ) 對(duì)AQP-1 表達(dá)的影響。方法 40 只C57BL/6 小鼠隨機(jī)分對(duì)照組( A 組) 、AZ 大劑量干預(yù)組( 300 mg/kg, B 組) 、AZ 中劑量干預(yù)組( 200 mg/kg, C 組) 、AZ 小劑量干預(yù)組( 100 mg/kg, D 組) 和哮喘組( E 組) , 每組8 只。干預(yù)組在激發(fā)階段給予不同劑量的AZ 腹腔注射。結(jié)果 ①E 組肺組織的濕干重比值比A 組明顯增高( P lt;0. 05) ; B、C、D組肺組織的濕干重比值較E 組顯著減低( P lt;0. 05) , 與劑量呈負(fù)相關(guān)性。②E 組BALF 中細(xì)胞總數(shù)、嗜酸粒細(xì)胞數(shù)和IL-5 水平均高于A 組( P lt; 0. 05) ,IFN-γ水平低于A 組( P lt;0. 05) , 治療后細(xì)胞總數(shù)、嗜酸粒細(xì)胞數(shù)、中性粒細(xì)胞及淋巴細(xì)胞均明顯下降( P lt;0. 05) , 且與劑量呈正相關(guān)性。③E 組AQP-1 在氣管黏膜上皮、微血管內(nèi)膜上皮、支氣管周圍血管床及炎癥細(xì)胞呈強(qiáng)陽(yáng)性表達(dá), 其表達(dá)水平明顯高于A 組( P lt;0. 01) , 使用AZ 干預(yù)后表達(dá)明顯低于
E 組( P lt;0. 05) , 下降的幅度與劑量呈正相關(guān)性; 但AQP-1 mRNA 檢測(cè)結(jié)果無(wú)明顯差異( P gt; 0. 05) 。結(jié)論 ①AQP-1 在急性哮喘小鼠肺組織內(nèi)及炎癥細(xì)胞上過(guò)度表達(dá), E 組呈強(qiáng)陽(yáng)性表達(dá)。②AZ 對(duì)AQP-1 有顯著的抑制作用, 可明顯改善小鼠肺部的炎性細(xì)胞浸潤(rùn)等病理改變, 且呈劑量依賴性。③AQP-1蛋白質(zhì)在各組中表達(dá)差異較大, 但AQP-1 mRNA 無(wú)明顯差異, 提示乙酰唑胺對(duì)AQP-1 的影響可能是在轉(zhuǎn)錄后的水平上。
引用本文： 唐順廣,周瑞祥,賁素琴,倪松石. 急性哮喘小鼠肺組織水通道蛋白1 的表達(dá)變化及乙酰唑胺對(duì)其表達(dá)的影響. 中國(guó)呼吸與危重監(jiān)護(hù)雜志, 2010, 9(3): 268-272. doi: 復(fù)制
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- 1. 王吉耀, 主編. 內(nèi)科學(xué). 北京: 人民衛(wèi)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. 關(guān)桂梅, 董震, 呂梅, 等. 鼻息肉組織嗜酸粒細(xì)胞中水通道蛋白-1 和抗凋亡基因Bcl-2 mRNA 的表達(dá)及意義. 中華耳鼻咽喉頭頸外科雜志, 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. 沈華浩, 王蘋(píng)莉. 如何評(píng)價(jià)哮喘動(dòng)物模型. 醫(yī)學(xué)與哲學(xué)( 臨床決策論壇版) , 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.