特发性肺纤维化患者支气管肺泡灌洗液和血清基质金属蛋白酶及其抑制剂检测

目的探讨特发性肺纤维化(IPF)患者支气管肺泡灌洗液(BALF)及血清中基质金属蛋白酶9(MMP9)、基质金属蛋白酶组织抑制剂1(TIMP1)水平的变化。方法2001至2004年用酶联免疫吸附(ELISA)法检测30例IPF患者BALF及血清中MMP9和TIMP1的水平,同时行肺高分辨率CT(HRCT)及肺功能检查。健康非吸烟的自愿献血者30名,为血清对照组。以胸痛为自觉症状在我院自愿进行纤维支气管镜及BALF检查,经体检及X线检查证实为健康者13名,作为BALF对照组。结果IPF患者BALF及血清中MMP9水平为(245±26)和(203±32)ng/L,对照组为(205±22)和(186±16)ng/L,两组相比差异无统计学意义;IPF组BALF及血清中TIMP1水平[(522±81)、(166±29)ng/L]高于对照组[(201±31)、(87±16)ng/L],差异有统计学意义;IPF组BALF及血清中MMP9/TIMP1比值(0.53±0.18,1.5±0.3)低于对照组(1.06±0.38,2.6±0.5)。HRCT、肺功能评分及BALF中上述指标与MMP9无明显相关性,与TIMP1呈正相关,与MMP9/TIMP1比值呈负相关。结论IPF患者肺纤维化的发生与TIMP1水平升高及MMP9/TIMP1比值降低对细胞外基质降解的抑制有关,后者可能意义更大;患者肺影像学及肺功能变化可能也与此有关。

Changes of matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 in the bronchoalveolar lavage fluid and the serum of patients with idiopathic pulmonary fibrosis

OBJECTIVE: To detect the levels of matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in the bronchoalveolar lavage fluid (BALF) and the serum of patients with idiopathic pulmonary fibrosis (IPF), and to evaluate the significance of the changes in the pathogenesis of IPF. METHODS: Enzyme-linked immunoadsordent assay (ELISA) was used to detect MMP-9 and TIMP-1 in the BALF and serum of 30 patients with IPF. RESULTS: The levels of MMP-9 in the BALF and serum of the patients showed no significant difference as compared with those of the control group. The levels of TIMP-1 in the BALF [(522 +/- 81) ng/L] and serum [(166 +/- 29) ng/L] of the patients were higher than those [(201 +/- 31), (87 +/- 16) ng/L] of the control group (P < 0.01). The ratios of MMP-9/TIMP-1 in the BALF (0.53 +/- 0.18) and serum (1.5 +/- 0.3) of patients with IPF were lower than those (1.06 +/- 0.38, 2.6 +/- 0.5) of the control group (P < 0.01, < 0.05). TIMP-1 in the BALF of the patients showed a strong positive correlation with chest CT fibrosis and pulmonary function test scores (P < 0.01), while MMP-9/TIMP-1 in the BALF had negative correlation with them (P < 0.01). CONCLUSION: Pulmonary fibrosis may be associated with increased TIMP-1 and decreased MMP-9/TIMP-1, which is able to inhibit the degradation of extracellular matrix.