基质金属蛋白酶及金属蛋白酶组织抑制剂在结核性胸膜炎中的发生情况

Occurrence of matrix metalloproteinases and tissue inhibitors of metalloproteinases in tuberculous pleuritis.

作者信息

Hoheisel G, Sack U, Hui D S, Huse K, Chan K S, Chan K K, Hartwig K, Schuster E, Scholz G H, Schauer J

机构信息

Pulmonary and Endocrinology Units, University of Leipzig, Germany.

出版信息

Tuberculosis (Edinb). 2001;81(3):203-9. doi: 10.1054/tube.2000.0276.

DOI:10.1054/tube.2000.0276

PMID:11466032

Abstract

OBJECTIVE

Matrix metalloproteinases (MMP) and tissue inhibitors of metalloproteinases (TIMP) have been found in high concentrations in pleural effusions. Because MMP and TIMP may play a part in the causation of the fibrosis seen in tuberculous (TB) pleuritis their occurrence was examined.

DESIGN

Pleural effusion fluid and plasma concentrations of MMP-1, MMP-2, MMP-3, MMP-8, MMP-9, TIMP-1 and TIMP-2 were determined by ELISA in 21 patients with TB pleuritis. To adjust for the total protein content, respective ratios were calculated. Activities of MMP-2 and MMP-9 were measured by gelatine zymography and the MMP-9/MMP-2 ratios calculated. Pleural effusions and plasma of 15 patients with congestive heat failure (CHF) and plasma of 15 healthy persons (CON) served as controls.

RESULTS

Immunoreactive pleural fluid concentrations of MMP-1, MMP-2, MMP-8, and MMP-9 were higher in TB compared to CHF, but plasma concentrations were not different between the groups. TB pleural fluid concentrations of MMP-1, MMP-2, TIMP-1, and TIMP-2 were higher compared to TB plasma. MMP-3 was found in trace amounts only. The MMP-9/total protein ratios in pleural fluid were higher in TB compared to CHF (0.4492+/-0.1633 vs 0.0364+/-0.0145, P<0.005) but the TIMP-1 ratios were lower (139.0+/-28.7 vs 517.8+/-183.7, P<0.0005). In TB pleural fluid vs TB plasma, the respective MMP-1, MMP-2, TIMP-1, and TIMP-2 ratios were increased (0.46+/-0.10 vs 0.17+/-0.02; 25.2+/-2.8 vs 4.2+/-0.9; 139.0+/-28.7 vs 27.8+/-8.2; 0.67+/-0.13 vs 0.18+/-0.04, P<0.0005 each). Gelatine zymography demonstrated MMP-2 and MMP-9 bands of different brightness in TB effusions but in CHF effusions the MMP-9 band was barely visible. The MMP-9/MMP-2 effusion ratios were therefore higher in TB compared to CHF (0.46+/-0.15 vs 0.05+/-0.04, P<0.0005).

CONCLUSION

Compartmentalized MMP-1, MMP-2, TIMP-1, and TIMP-2 and, compared to CHF, a surplus of MMP-1, MMP-2, MMP-8, and MMP-9 in the pleural space obviously contribute to the fibrotic reactions in TB pleuritis.

摘要

目的

已发现基质金属蛋白酶（MMP）和金属蛋白酶组织抑制剂（TIMP）在胸腔积液中浓度很高。由于MMP和TIMP可能在结核性胸膜炎中所见的纤维化病因中起作用，因此对它们的出现情况进行了检查。

设计

采用酶联免疫吸附测定法（ELISA）测定了21例结核性胸膜炎患者胸腔积液和血浆中MMP-1、MMP-2、MMP-3、MMP-8、MMP-9、TIMP-1和TIMP-2的浓度。为校正总蛋白含量，计算了各自的比值。测定了15例充血性心力衰竭（CHF）患者的胸腔积液和血浆以及15名健康人（CON）的血浆作为对照。

结果

与CHF相比，结核性胸膜炎患者胸腔积液中MMP-1、MMP-2、MMP-8和MMP-9的免疫反应性浓度更高，但两组间血浆浓度无差异。与结核性胸膜炎患者血浆相比，其胸腔积液中MMP-1、MMP-2、TIMP-1和TIMP-2的浓度更高。仅发现痕量的MMP-3。与CHF相比，结核性胸膜炎患者胸腔积液中MMP-9/总蛋白比值更高（0.4492±0.1633对0.0364±0.0145，P<0.005），但TIMP-1比值更低（139.0±28.7对517.8±183.7，P<0.0005）。与结核性胸膜炎患者血浆相比，其胸腔积液中MMP-1、MMP-2、TIMP-1和TIMP-2的各自比值升高（0.46±0.10对0.17±0.02；25.2±2.8对4.2±0.9；139.0±28.7对27.8±8.2；0.67±0.13对0.18±0.04，P均<0.0005）。明胶酶谱法显示结核性胸膜炎患者胸腔积液中有亮度不同的MMP-2和MMP-9条带，但在CHF患者胸腔积液中MMP-9条带几乎不可见。因此，与CHF相比，结核性胸膜炎患者胸腔积液中MMP-9/MMP-2比值更高（0.46±0.15对0.05±0.04，P<0.0005）。