摘要 目的通过建立哮喘大鼠模型，观察气道结构改变，探讨促血管生成素1（Ang1）及其受体(Tie2)在哮喘大鼠气道中的表达和意义以及地塞米松对其的影响。方法SpragueDawley大鼠 45只，随机分为对照组，模型组和地塞米松干预组。采用腹腔注射10%卵清蛋白致敏和1%卵清蛋白雾化吸入激发复制哮喘模型，干预组每次激发前给予地塞米松。采用免疫组化检测Ang1及其受体Tie2在不同组间气道壁表达变化；采用计算机病理图像分析系统分析各组气道壁厚度。结果①模型组气道壁厚度较对照组明显增加（33.9333±8.3791 μm2/μm vs 21.1333±2.7740μm2/μm，P<0.01），干预组为（27.4000±4.6105 μm2/μm）较对照组增加（P<0.01），但较模型组明显减轻（P<0.01）。②模型组气道壁Ang1及其受体Tie2在气道上皮表达较对照组明显增加（103.9487±8.2914 vs 76.0320±3.7728，99.2307±8.1913 vs 75.3153±3.7321，P<0.01），干预组为（90.6180±5.2339，86.6633±3.7321）较对照组增加（P<0.01），但较模型组明显下降（P<0.01）。③直线相关分析显示气道壁Ang1及其受体Tie2的表达同气道壁厚度呈正相关，Ang1与其受体Tie2间也呈明显正相关，均 P<0.01。结论 哮喘模型大鼠气道壁中Ang1及其受体Tie2表达上调，并与气道壁厚度呈正相关，提示Ang1及其受体Tie2可能参与哮喘气道重建过程。地塞米松可下调Ang1与其受体Tie2在气道壁的表达，并可减轻气道结构改变。
Abstract：ObjectiveTo study the effect of dexamethasone on airway morphology and on the expression of angiopoietin1 (Ang1) and its tyrosine kinase receptor Tie2 in the airway of asthmatic rats.MethodsFortyfive SpragueDawley rats were randomly divided into control, asthmatic, and dexamethasonetreated asthmatic groups. Asthma was induced by repeated sensitization and challenge with ovalbumin in the latter two groups. The dexamethasone intervention group received an intraperitonea injection of dexamethasone (2 mg/kg) before asthma challenge. Immunohistochemistry was used to measure the expression of Ang1 and Tie2 in the airway. Airway thickness was estimated by a computerized digital image analyzer. ResultsAirway thickness in the asthmatic group (33.9333±8.3791 μm2/μm) increased significantly compared with that in the control group (21.1333±2.7740 μm2/μm) (P<0.01). The dexamethasone intervention group also showed increased thickness of the airway (27.4000 ± 4.6105 μm2/μm) compared with the control group (P<0.01), but the airway thickness in the dexamethasone intervention group was significantly reduced compared with that in the untreated asthmatic group (P<0.01). The expression of Ang1 (103.9487±8.2914 vs 76.0320±3.7728; P<0.01) and Tie2 (99.2307±8.1913 vs 75.3153±3.7321; P<0.01) in the airway increased significantly in the asthmatic group compared to controls. The expression of Ang1 and Tie2 in the airway of the dexamethasone intervention group (90.6180±5.2339 and 86.6633±3.7321, respectively) was statistically higher than that in the control group (P<0.01) but statistically lower than that in the untreated asthmatic group (P<0.01). Ang1 and Tie2 expression in the airway was positively correlated with the thickness of airway (rAng1=0.719，rTie2=0.746，P<0.01). There was also a positive correlation between Ang1 and Tie2 expression (r=0.742，P<0.01). ConclusionsThe expression of Ang1 and Tie2 in the airway increased in asthmatic rats and was positively correlated with the thickness of the airway. Ang1 and Tie2 may participate in the process of airway remodeling in asthma. Dexamethasone can decrease the expression of Ang1 and Tie2 in the airway and relieve the changes of airway morphology.
QIAO Dun-Yang,LUAN Bin,HAN Su-Ge et al. Expression of angiopoietin-1 and its tyrosine kinase receptor Tie-2 in the airway of asthmatic rats[J]. CJCP, 2008, 10(5): 642-646.
