基质金属蛋白酶9和基质金属蛋白酶组织抑制物1在不同性质胸腔积液诊断和鉴别诊断中的应用

Value of matrix metalioproteinase-9 and tissue inhibitor of metalloproteinase-1 in diagnosis and differential diagnosis of plenral effusion

目的探讨基质金属蛋白酶9（MMP-9）、基质金属蛋白酶组织抑制物1（TIMP-1）及MMP-9／TIMP-1比值在结核性和肿瘤性胸腔积液形成过程中的作用及在上述胸腔积液诊断和鉴别诊断中的价值。方法采用ELISA法测定36例结核性胸膜炎、38例恶性肿瘤和14例漏出液患者胸水中MMP-9和TIMP-1的浓度。结果①结核性胸腔积液组胸水中MMP-9浓度、TIMP-1浓度和MMP-9／TIMP—1比值均高于恶性胸腔积液组和漏出液组（P值均〈0．05），恶性胸腔积液组上述指标均高于漏出液组（P值均〈0．05）。②恶性胸水脱落细胞学检查阳性组MMP-9浓度、MMP-9／TIMP-1均高于细胞学检查阴性组（P值均〈0．05），TIMP-1浓度低于细胞学检查阴性组（P〈0．05）。③MMP-9和TIMP-1之间呈正相关（r=0．239，P=0．025）；MMP-9、MMP-9／TIMP-1分别与胸水乳酸脱氢酶、腺苷脱氨酶、蛋白质、白细胞总数、淋巴细胞比例之间呈显著正相关（P值均〈0．01）；MMP-9、MMP-9／TIMP—1分别与胸水葡萄糖、氯化物之间呈显著负相关（P值均〈0．01）；TIMP-1与乳酸脱氢酶、腺苷脱氨酶、蛋白质、淋巴细胞比例之间呈显著正相关（P值均〈0．01）。④胸水中MMP-9、TIMP-1、MMP-9／TIMP-1比值在恶性胸腔积液诊断中的敏感性分别为63．2％、71．1％和65．8％，特异性分别为83．3％、63．9％和80．6％。采用胸水MMP-9和TIMP-1串联联合检测的敏感性和特异性分别为39．5％和91．7％，并联联合检测的敏感性和特异性分别为94．7％和55．6％。结论MMP-9和TIMP-1与结核性胸膜炎和恶性胸腔积液的形成密切相关，MMP-9／TIMP-1比例的失衡在此过程中扮演了重要角色，胸水MMP-9、TIMP-1及MMP-9／TIMP-1比值的检测有助于结核性胸膜炎和恶性肿瘤所致胸腔积液的鉴别诊断。

Objective To explore the role of matrix metalloproteinase-9 （MMP-9） and tissue inhibitor of metalloproteinase-1 （TIMP-1） in the pathogenesis of tuberculous and tumorous pleural effusion,and to assess the value of MMP-9, TIMP-1 and MMP-9/TIMP-1 in the diagnosis and differential diagnosis of these two kinds of pleural effusion. Methods MMP-9 and TIMP-1 in the pleural fluid were detected by enzyme-linked immunosorbent assay in 36 patients with tuberculous pleuritis,38 patients with malignant tumor and 14 patients with transudates. Results ① MMP-9, TIMP-1 and MMP-9/TIMP-1 in tuberculous pleural effusion were higher than those in malignant pleural effusion and transudates （all P 〈0.05）. MMP-9, TIMP-1 and MMP-9/TIMP-1 in malignant pleural effusion were higher than those in transudates（all P 〈0.05）. ②MMP-9 and MMP-9/TIMP-1in malignant pleural effusion with positive cytological findings were higher than those with negative cytological findings（all P 〈0. 05） ,while TIMP-1 was lower in the former than that in the latter（ P 0.05）. ③MMP-9 positively correlated with TIMP-1 （ r = 0. 239, P = 0. 025）. MMP-9 and MMP-9/ TIMP-1 positively correlated with lactate dehydrogenase, adenosine deaminase, protein, total white blood cells and lymphocyte ratio in pleural effusion（all P ~ 0.01）, and negatively correlated with glucose and chloride in pleural effusion （all P 〈 0.01 ）. TIMP-1 positively correlated with lactate dehydrogenase, adenosine deaminase, protein and lymphocyte ratio in pleural effusion（all P 〈0.01 ）. ④ In diagnosing tumorous pleural effusion, the sensitivities of MMP-9, TIMP-1 and MMP-9/TIMP-1 were respectively 63. 2%, 71.1% and 65.8%0, the specificities were respectively 83.3 %, 63.9% and 80. 6%. However, in the diagnosing process, the sensitivity and specificity were 39.5% and 91.7% when MMP-9 and TIMP-1 were combined in a series way, 94.7% and 55.6% in a parallel way. Conclusions MMP-9 and TIMP-1 are closely related to the tuberculous and tumorous pleural effusion. MMP-9/TIMP-1 plays a great role in the pathogenesis of tuberculous and tumorous pleural effusion. Detection of MMP-9, TIMP-1 and MMP-9/TIMP-1 in pleural effusion contributes to the differential diagnosis of tuberculous pleurisy and malignant pleural effusion.