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目的探讨基质金属蛋白酶9(MMP9)及其组织抑制物(TIMP1)在支气管哮喘发病中的作用,评价吸入糖皮质激素对其调节作用。方法建立哮喘大鼠模型,用ELISA、免疫组织化学、westernblot及RTPCR技术,对激素治疗前后哮喘大鼠肺组织中MMP9及TIMP1表达进行研究。结果(1)通过大鼠行为学改变、呼吸功能曲线、IgE水平以及肺组织切片证实哮喘模型成立。(2)哮喘组肺组织细小支气管壁及伴行动脉周围炎性细胞浸润,黏膜断裂,杯状细胞增生,平滑肌增厚;21天组气道壁基膜增厚和平滑肌增生更加明显。(3)大鼠肺组织MMP9mRNA表达:哮喘7天组为(2.71±0.37),21天组为(1.76±0.27),激素治疗组为(0.88±0.18),正常对照组为(0.52±0.10),组间比较差异有统计学意义(F=151.52,P<0.01)。大鼠肺组织TIMP1mRNA表达:哮喘7天组为(1.13±0.19),21天组为(1.55±0.24),激素治疗组为(0.77±0.15),正常对照组为(0.47±0.08),组间比较差异有统计学意义(F=69.46,P<0.01)。(4)免疫组织化学及蛋白质表达结果与RTPCR结果一致。结论从蛋白质水平及mRNA水平证实哮喘大鼠模型肺组织MMP9表达升高,TIMP1表达亦增强;激素下调MMP9及TIMP1表达,可能是其抑制气道炎症和气道重塑的机制之一。
Objective To investigate the role of matrix metalloproteinase 9 (MMP9) and its tissue inhibitor of metalloproteinase (TIMP1) in the pathogenesis of bronchial asthma and to evaluate the effect of inhaled corticosteroids on it. Methods The asthmatic rat model was established. The expression of MMP9 and TIMP1 in the lung tissue of asthmatic rats before and after hormone treatment was studied by ELISA, immunohistochemistry, western blot and RTPCR. Results (1) The model of asthma was confirmed by behavioral changes, respiratory function curve, IgE level and lung tissue sections. (2) Inflammatory cell infiltration, mucosal rupture, goblet cell hyperplasia and smooth muscle thickening in the bronchial wall and accompanying artery in the asthma group were more obvious. In the 21-day group, the thickening of the basement membrane of the airway wall and smooth muscle hyperplasia were more obvious. (3) The expression of MMP9mRNA in rat lung tissue was (2.71 ± 0.37) in 7d asthma group and (1.76 ± 0.27) in 21d group, (0.88 ± 0.18) in hormonal treatment group and (0.52 ± 0.10) in normal control group , The difference between the groups was statistically significant (F = 151.52, P <0.01). The expression of TIMP1mRNA in the lung tissue of rats was (1.13 ± 0.19) days in asthma group and (1.55 ± 0.24) in 21 days group, (0.77 ± 0.15) in hormonal therapy group and (0.47 ± 0.08) in normal control group, The difference was statistically significant (F = 69.46, P <0.01). (4) Immunohistochemistry and protein expression results were consistent with RTPCR results. Conclusions The expression of MMP9 and the expression of TIMP1 in the lung tissue of asthmatic rats were confirmed by protein and mRNA levels. Hormone down-regulation of MMP9 and TIMP1 may be one of the mechanisms of airway inflammation and airway remodeling.