【摘要】 目的:探讨基质金属蛋白酶(MMP-9),组织金属蛋白酶抑制物(TIMP-1)在哮喘大鼠发病中的作用及与气道重塑的关系.方法:将20只幼年Wistar大鼠随机分为正常对照组、哮喘模型组,每组10只.采用卵蛋白(OVA)等致敏大鼠哮喘模型,第14日后用10 g/L卵蛋白溶液雾化吸入,20 min激发,1次/d,持续6 wk;对照组用生理盐水雾化吸入.观察两组动物哮喘发作症状、气道壁厚度、平滑肌层厚度及胶原沉积情况;免疫组化染色检测MMP-9和TIMP-1的表达;ELISA检测血清、肺泡灌洗液中MMP-9和TIMP-1水平,并了解其与组织表达量的相关性.结果:哮喘模型组肺组织MMP-9,TIMP-1表达明显降低,其气道壁、平滑肌的厚度明显大于正常对照组,其血清和肺泡灌洗液的水平明显高于正常对照组,差异具有显著性统计学意义(P<0.01).血清和肺泡灌洗液的MMP-9,TIMP-1水平与气道壁的厚度、平滑肌层的厚度以及胶原面积呈正相关,与组织中MMP-9,TIMP-1的表达成负相关.结论:MMP-9,TIMP-1参与了气道重塑的过程;检测血清和肺泡灌洗液中MMP-9和TIMP-1的水平对哮喘的临床诊断具有指导意义.更多还原

【Abstract】 AIM: To explore the roles of matrix metalloproteinase 9(MMP-9) and tissue inhibitor metalloproteinase 1(TIMP-1) in the morbidity of asthma and their relation with airway remodeling.METHODS: Twenty young Wistar rats were randomly divided into normal control group and asthma model group,with 10 in each group.Ovalbumin(OVA) was adopted for sensitizing asthma rat model.After 14 d,1% ovalbumin solution aerosol was given to rats of asthma model group,which had been excited for 20 min,once daily for 6 weeks.Aerosol inhalation with normal saline was adopted for control group.Asthmatic attack symptoms,airway wall thickness,thickness of smooth muscle and collagen deposition were observed in each group.MMP-9 and TIMP-1 levels in serum and BALF of experimental rats were detected by ELISA and their relationship with MMP-9 and TIMP-1 expression in lung tissues was analyzed.RESULTS: MMP-9 and TIMP-1 expression was reduced significantly in lung tissues of asthma model and their airway walls and smooth muscle thickness were significantly higher than those in control group.The serum and BALF MMP-9 and TIMP-1 levels were significantly higher in asthma model than those in normal control group,with statistically significant difference.MMP-9 and TIMP-1 levels in serum and BALF were positively correlated with airway wall thickness,smooth muscle thickness and collagen area,and negatively correlated with MMP-9 and TIMP-1 expression in lung tissues.CONCLUSION: MMP-9 and TIMP-1 are involved in the airway remodeling process.MMP-9 and TIMP-1 levels in serum and BALF are of some significance for clinical diagnosis.更多还原