地塞米松对哮喘大鼠气道重塑及基质金属蛋白酶-9表达的影响

目的　探讨哮喘大鼠气道重塑与基质金属蛋白酶 9(MMP 9)表达的关系以及地塞米松的干预作用。方法　建立大鼠哮喘模型 ,采用免疫组化技术结合计算机病理图像分析系统 ,测定 3组大鼠气道形态学参数及支气管上皮细胞MMP 9、基质金属蛋白酶组织抑制剂 1 (TIMP 1 )的相对含量。结果　哮喘组支气管总管壁厚度和平滑肌厚度明显高于对照组 (P <0 .0 1 )和地塞米松组 (P分别 <0 .0 5 ,<0 .0 1 ) ;哮喘组MMP 9、TIMP 1在气道黏膜上皮的表达量明显高于对照组 (P <0 .0 1 )和地塞米松组 (P分别 <0 .0 1 ,<0 .0 5 ) ;哮喘组MMP 9 TIMP 1比例失衡。结论　吸入地塞米松可抑制气道壁和平滑肌厚度的增加 ;MMP 9过度表达、MMP 9 TIMP 1比例失衡在哮喘气道重塑发生机制中发挥重要作用 ;地塞米松可能通过下调MMP 9的表达 ,调节MMP 9 TIMP 1之间的平衡 ,干预气道重塑

Effect of dexamethasone on airway remodelling and expression of matrix metalloproteinases-9 in asthmatic rats

Objective To explore the relationship between airway remodelling and expression of MMP 9 and the effect of dexamethasone in asthmatic rats.Methods Asthmatic model was established using rats.The changes of airway wall morphologic parameter and the relative content of MMP 9,TIMP 1 in bronchial epithelium in the three groups were determined using immunohistochemical technique and a computer assisted image analysis system.Results The thickness of total airway wall and smooth muscle in asthmatic group were higher those that in control group ( P <0.01)and dexamethasone(DXM) group ( P <0.05,<0.01,respectively).The amount of MMP 9 and TIMP 1 expression in bronchial epithlium in asthmatic group were higher than those in control group ( P <0.01)and DXM group( P <0.01,<0.05,respectively).The imbalance between MMP 9 and TIMP 1 was observed.Conclusion Inhaling DXM may restrain the increase of thickness of total airway wall and smooth muscle. The excessive expression of MMP 9 and the imbalance between MMP 9 and TIMP 1 play important roles in the pathogenesis of airway remodelling in asthma.DXM can influence airway remodelling by downregulating the expression of MMP 9 and regulating the balance between MMP 9 and TIMP 1.