地塞米松对支气管哮喘大鼠气道重塑及内皮素-1的影响

目的观察哮喘大鼠血浆内皮素-1与气道重塑的关系及早晚期使用地塞米松的差异。方法40只大鼠随机分为对照组、模型组、早期干预组、晚期干预组,每组10只。以卵白蛋白致敏并吸入激发制备大鼠哮喘模型。模型组于第1、8天注射卵白蛋白(100g/L),第15天始雾化卵白蛋白(10g/L),20min/d。早期干预组同模型组,但雾化卵白蛋白前1h腹腔注射地塞米松,晚期干预组雾化卵白蛋白2周后注射地塞米松,对照组雾化与注射均用生理盐水代替。连续雾化8周。采用特异性放射免疫技术测定大鼠血浆内皮素-1含量。各组大鼠肺组织切片苏木精-伊红染色,计算机彩色图像分析测量大鼠气道形态学参数。结果早期干预组血浆内皮素-1水平高于对照组且低于哮喘组和晚期干预组(P<0.05)。早期干预组平滑肌厚度、总管壁厚度均高于对照组,均明显低于哮喘及晚期干预组(P<0.01)。结论内皮素-1在哮喘气道重塑中有重要作用。地塞米松可抑制气道壁和平滑肌厚度,早期使用可以延缓但不能逆转气道重塑。

Objective To explore the relationship between airway remodeling and expression of ET-1 and the effect of dexamethasone in asthmatic rats and compare the therapeutic differences between early phase and late phase. Methods Forty rats were randomly divided into 4 groups： control group, asthma group, early stage interventional group with dexamethasone and late stage interventional group with dexamethasone. Each group contained 10 rats. Asthmatic model was established using egg protein. In the asthma group,100g/L egg protein was intraperitoneally injected into rats on the first and eighth day,10g/L egg protein was atomized on the 15th day, once per day,20min per once. In the early stage interventional group, the procedure was the same as that of asthma group and dexamethasone was intraperitoneally injected at one hour of each atomization of egg protein. In the late stage interventional group with dexamethasone, two weeks after asthmatic model establishing, dexamethasone was intraperitoneally injected at one hour of each atomization of egg protein. The control group used normal saline instead of egg protein. Eight weeks of successive atomization was performed in each group, radioimmunity method was used in measuring the level of endothelin- 1. Lung tissue section was stained by haematoxylin and eosin in each group. The changes of airway wall morphologic parameter were determined using a computer assisted image analysis system. Results After 8 weeks of successive atomization, the expression of ET-1 in plasma in early stage interventional group stronger than in control group （P〈0.05）,and which was weaker in late stage interventional group than in asthma group and late stage interventional group （P〈0.05）. The thickness of total airway wall and smooth muscle in early stage treatment group were higher than those that in control group （P〈0.01） and lower than in asthma group and late stage treatment group （P〈0.01）. Conclusion ET-1 plays an important role in airway remodeling in asthma. Dexamethasone may restrain the increase of thickness of total airway wall and smooth muscle. Early treatment could postpone airway remodeling progress but could not reverse the established airway remodeling.