基质金属蛋白酶9及其抑制剂在慢性阻塞性肺疾病发病中的作用

目的　探讨基质金属蛋白酶 9(MMP 9)及其基质金属蛋白酶组织抑制剂 1(TIMP 1)在慢性阻塞性肺疾病 (COPD)发病机制中的作用。方法　选择COPD稳定期组 12例、COPD急性加重期组 12例、COPD急性加重期 +糖皮质激素治疗组 12例和正常对照组 12例患者 ,采用逆转录 聚合酶链的方法测定各组患者外周血单个核细胞中MMP 9和TIMP 1mRNA的表达 ,同时用明胶图谱法测定血浆中MMP 2 ,9的蛋白质水平 ,并分析其与肺功能的关系。结果　 (1)COPD各组MMP 9mRNA表达水平和MMP 9/TIMP 1的比值增加 ,与正常组相比 ,差异具有显著性 (P <0 0 5 ) ,而COPD各组间表达差异无显著性 (P >0 0 5 )。 (2 )COPD各组血浆中MMP 9蛋白水平增加 ,高于正常组 (P <0 0 5 ) ,而COPD各组间蛋白质水平差异无显著性 (P >0 0 5 )。 (3)COPD组中MMP 9mRNA的表达、MMP 9/TIMP 1比值及血浆中MMP 9蛋白质水平与FEV 1 0%占正常预计值呈负相关 (r =- 0 789,P <0 0 5 ;r =- 0 5 3,P <0 0 5 ;r =- 0 6 5 2 ,P <0 0 5 ) ,与RV/TLC %呈正相关 (r =0 375 ,P <0 0 5 ;r =0 4 4 ,P <0 0 5 ;r =0 5 2 9,P <0 0 5 )。结论　MMP 9和MMP 9/TIMP 1比例失衡在COPD的发病机制中起到了一定的作用 ,并与FEV1 0 %占正常预计值、RV/TLC %呈相关性。

The role of matrix metalloproteinases-9 and tissue inhibitor of metalloproteinaes-1 in chronic obstructive pulmonary disease

Objective To evaluate the role of matrix metalloproteinases-9 (MMP-9) and tissue inhibitor of metalloproteinases-1 (TIMP-1) in the pathogenesis of chronic obstructive pulmonary disease (COPD). Methods Five milliliters of peripheral venous blood were extracted form 36 patients with COPD, subdivided into stable group (CS group, n =12), exacerbation group (CE group, n =12), and exacerbation group with glucocorticosteroids treatment (CE + G group, n =12), and 12 normal controls. The peripheral blood mononuclear cells (PBMCs) were isolated and the mRNA expressions of MMP-9 and TIMP-1 therein in each group were measured by RT-PCR quantitative analysis. The MMP-2 and MMP-9 levels in the plasma were studied by gelatin zymography. The relationship between MMP and pulmonary function was evaluated. Results (1) The MMP-9 mRNA expression and MMP-9: TIMP-1 ratios in the samples obtained from patients with COPD were higher in comparison with those from the control group (all P <0.05). (2) The MMP-9 levels in plasma were higher in the COPD groups than in the control group ( P <0.05). (3) In the COPD groups, the MMP-9 mRNA expression, MMP-9:TIMP-1 ratio, and MMP-9 level in plasma were negatively correlated with FEV 1.0 % of prediction ( r =-0.789, P <0.05; r = -0.53, P <0.05; and r =-0.652, P <0.05), and positively correlated with RV/TLC%( r =0.375, P <0.05; r =0.44, P <0.05; and r =0.529, P <0.05). Conclusion MMP-9 and the imbalanced ratio of MMP-9: TIMP-1 may not only play a role in the pathogenesis of COPD, but also relate to FEV 1.0 % of prediction and RV/TLC%.