基质金属蛋白酶9和肿瘤坏死因子α表达与大鼠上下呼吸道炎性反应一致性研究

Role and mechanism of the expression of matrix metalloproteinase 9 and tumor necrosis factor α in upper and lower respiratory tract inflammation in rats

目的 通过建立变应性鼻炎（allergic rhinitis,AR）和支气管哮喘（简称哮喘,asthma,AS）动物模型,探讨基质金属蛋白酶9（matrix metalloproteinase-9,MMP-9）和肿瘤坏死因子α（tumor necrosis factor,TNF-α）在上下呼吸道炎性反应一致性中的作用及机制.方法 以卵清蛋白辅以氢氧化铝致敏并激发制成AR和AS大鼠模型.HE染色和甲苯胺蓝染色分别检测AR和AS大鼠模型鼻黏膜及肺组织中嗜酸粒细胞、肥大细胞的表达,免疫组化SP法检测上述组织中MMP-9和TNF-α的表达,分析嗜酸粒细胞、肥大细胞、MMP-9和TNF-α表达与上下呼吸道炎性反应的关系.采用SPSS13.0软件对数据进行统计学分析.结果 MMP-9阳性细胞数在AR组鼻黏膜和肺组织中分别为 （154.8±12.0）、（124.0±8.2）个,在AR对照组分别为（43.2±7.6）、（34.5±5.0）个,差异有统计学意义（t值分别为24.260、29.525,P值均＜0.05）;MMP-9阳性细胞数在AS组鼻黏膜和肺组织中分别为（149.9±11.7）、（120.1±7.3）个,在AS对照组分别为（48.6±7.6）、（39.1±5.2）个,差异有统计学意义（t值分别为22.929、28.530,P值均＜0.05）.TNF-α阳性细胞数在AR组鼻黏膜和肺组织中分别为（188.8±17.0）、（134.8±7.9）个,在AR对照组分别为（57.6±23.3）、（40.3±8.2）个,差异有统计学意义（t值分别为13.836、26.220,P值均＜0.05）;TNF-α阳性细胞数在AS组鼻黏膜和肺组织中分别为（179.2±15.4）、（153.5±10.1）个,在AS对照组分别为（70.5±33.1）、（33.8±14.0）个,差异有统计学意义（t值分别为9.412、21.858,P值均＜0.05）.MMP-9与TNF-α在AR组鼻黏膜及肺组织中的表达分别呈正相关（r值分别为0.893和0.700,P值分别为0.001和0.024）,二者在AS组鼻黏膜或肺组织中的表达分别呈正相关（r值分别为0.692和0.644,P值分别为0.027和0.044）.结论 上下呼吸道炎性反应具有一致性,MMP-9和TNF-α可能在上下呼吸道炎性反应一致性中发挥重要作用.

Objective To investigate the role and mechanism of matrix metalloproteinase 9（MMP-9） and tumor necrosis factor α （TNF-α） in the pathogenesis of allergic rhinitis （AR） and asthma （AS）. Methods The rat models of AR and AS were made by injecting ovalbumin. The infiltration of eosinophils and mast cells were detected by hematoxylin-eosin （HE） staining and toluidine blue staining respectively, and the expression of MMP-9 and TNF-α in nasal mucosa and lung tissue were examined by immunohistochemical staining （ SP method）. The relationship of their expression with upper and lower respiratory tract inflammation was analyzed. SPSS 13.0 software was used to analyze the data. Results The numbers of MMP-9 positive inflammatory cells in nasal mucosa and lung tissue of AR were （ 154.8±12.0）and （124. 0 ±8.2）, （43. 2 ±7.6） and （34. 5 ±5.0） in the control groups, the difference was significant （t value were 24. 260, 29. 525 respectively, all P＜0.05）. The numbers of MMP-9 positive inflammatory cells in nasal mucosa and lung tissue of AS were （149.9±11.7）and（120.1±7.3）, （48.6 ± 7. 6） and （39.1±5.2）in control groups, the difference was significant （t value were 22. 929 and 28. 530respectively, all P＜0.05）.The numbers of TNF-α positive inflammatory cells in nasal mucosa and lung tissue of AR were （188.8±17.0）, and （134.8±7.9）, （57.6±23.3）and（40. 3 ± 8. 2 ） in control groups, the difference was significant （t value were 13. 836 and 26. 220, all P ＜0.05）. The numbers of TNF-α positive inflammatory cells in nasal mucosa and lung tissue of AS were （179. 2 ± 15.4 ） and （ 153. 5 ± 10. 1 ）, （70. 5 ±33. 1 ） and （ 33.8 ± 14. 0） in control groups, the difference was significant （ t value were 9. 412 and 21. 858, all P ＜0. 05）. There was a correlation between the expression of MMP-9 and TNF-α in nasal mucosa and lung tissue of AR （ r values were 0. 893 and 0. 700 respectively, P values were 0. 001 and 0. 024, respectively ） and AS （ r values were 0. 692 and 0. 644 respectively, P values were 0. 027and 0. 044 respectively） groups. Conclusions The inflammation is similar between AR and AS. The MMP9 and TNF-α may play an important role in the pathogenesis of upper and lower respiratory tract inflammation.