促血管生成素-1及其受体Tie-2在哮喘大鼠气道中的表达

Expression of angiopoietin-1 and its tyrosine kinase receptor Tie-2 in the airway of asthmatic rats

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（Ang1）及其受体(Tie2)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SpragueDawley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Ang1及其受体Tie2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Ang1及其受体Tie2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Ang1及其受体Tie2的表达同气道壁厚度呈正相关，Ang1与其受体Tie2间也呈明显正相关，均 P<0.01。结论 哮喘模型大鼠气道壁中Ang1及其受体Tie2表达上调，并与气道壁厚度呈正相关，提示Ang1及其受体Tie2可能参与哮喘气道重建过程。地塞米松可下调Ang1与其受体Tie2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 angiopoietin1 (Ang1) and its tyrosine kinase receptor Tie2 in the airway of asthmatic rats.MethodsFortyfive SpragueDawley rats were randomly divided into control, asthmatic, and dexamethasonetreated 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 Ang1 and Tie2 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 Ang1 (103.9487±8.2914 vs 76.0320±3.7728; P<0.01) and Tie2 (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 Ang1 and Tie2 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). Ang1 and Tie2 expression in the airway was positively correlated with the thickness of airway (rAng1=0.719，rTie2=0.746，P<0.01). There was also a positive correlation between Ang1 and Tie2 expression (r=0.742，P<0.01). ConclusionsThe expression of Ang1 and Tie2 in the airway increased in asthmatic rats and was positively correlated with the thickness of the airway. Ang1 and Tie2 may participate in the process of airway remodeling in asthma. Dexamethasone can decrease the expression of Ang1 and Tie2 in the airway and relieve the changes of airway morphology.