Matrix metalloproteinase-9, -10, and tissue inhibitor of matrix metalloproteinases-1 blood levels as biomarkers of severity and mortality in sepsis.
Matrix metalloproteinase-9, -10, and tissue inhibitor of matrix metalloproteinases-1 blood levels as biomarkers of severity and mortality in sepsis.
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DOI：
10.1186/cc8115
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发表时间：
2009
期刊：
影响因子：
--
通讯作者：
Páramo JA
中科院分区：
文献类型：
--
作者：
Lorente L;Martín MM;Labarta L;Díaz C;Solé-Violán J;Blanquer J;Orbe J;Rodríguez JA;Jiménez A;Borreguero-León JM;Belmonte F;Medina JC;Llimiñana MC;Ferrer-Agüero JM;Ferreres J;Mora ML;Lubillo S;Sánchez M;Barrios Y;Sierra A;Páramo JA
基质金属蛋白酶 (MMP) 通过细胞外基质 (ECM) 降解在传染病中发挥作用，这有利于免疫细胞从血流迁移到炎症部位。尽管在小范围脓毒症患者中发现了较高水平的 MMP-9 和基质金属蛋白酶组织抑制剂 - 1 (TIMP-1)，但尚未在这种情况下研究 MMP-10 水平。本研究的目的是确定 MMP-9、MMP-10 和 TIMP-1 对大量严重脓毒症患者的临床严重程度和死亡率的预测价值。这是一项在六个西班牙重症监护病房进行的多中心、观察性和前瞻性研究。我们在研究中纳入了 192 名严重脓毒症患者（125 名存活者和 67 名死亡者）和 50 名年龄和性别匹配的健康对照者。在诊断时测量严重脓毒症患者和健康对照者的 MMP-9、MMP-10、TIMP-1、肿瘤坏死因子 (TNF)-α 和白细胞介素 (IL)-10 的血清水平。与健康对照相比，脓毒症患者的 MMP-10 和 TIMP-1 水平较高，MMP-10/TIMP-1 比值较高，MMP-9/TIMP-1 比值较低（P < 0.001）。通过 SOFA 评分、APACHE-II 评分、乳酸、血小板计数和凝血病标志物评估，MMP-9、MMP-10、TIMP-1 和 MMP-9/TIMP-1 比率与脓毒症严重程度参数之间存在关联。与存活患者相比，未存活脓毒症患者的 MMP-9 水平较低（P = 0.037），TIMP-1 水平较高（P < 0.001），MMP-9/TIMP-1 比值较低（P = 0.003），IL-10 水平较高（P < 0.001），TNF-α/IL-10 比值较低。研究发现 MMP-9、MMP-10 和 TIMP-1 水平以及 TNF-α 和 IL-10 水平之间存在关联。 TIMP-1值大于531 ng/ml的脓毒症患者的死亡风险比值较低的患者高80%（RR = 1.80；95% CI = 1.13至2.87；P = 0.01；敏感性= 0.73；特异性= 0.45）。我们对严重脓毒症患者的研究的新发现（据我们所知，关于脓毒症 MMP 水平的最大系列报告数据）是，MMP-9/TIMP-1 比率降低和 MMP-10 水平升高可能对严重脓毒症的严重程度和死亡率具有重要的病理生理学意义，并且 TIMP-1 水平可能代表预测脓毒症患者临床结果的生物标志物。
Matrix metalloproteinases (MMPs) play a role in infectious diseases through extracellular matrix (ECM) degradation, which favors the migration of immune cells from the bloodstream to sites of inflammation. Although higher levels of MMP-9 and tissue inhibitor of matrix metalloproteinases-1 (TIMP-1) have been found in small series of patients with sepsis, MMP-10 levels have not been studied in this setting. The objective of this study was to determine the predictive value of MMP-9, MMP-10, and TIMP-1 on clinical severity and mortality in a large series of patients with severe sepsis. This was a multicenter, observational, and prospective study carried out in six Spanish Intensive Care Units. We included 192 (125 surviving and 67 nonsurviving) patients with severe sepsis and 50 age- and sex-matched healthy controls in the study. Serum levels of MMP-9, MMP-10, TIMP-1, tumor necrosis factor (TNF)-alpha, and interleukin (IL)-10 were measured in patients with severe sepsis at the time of diagnosis and in healthy controls. Sepsis patients had higher levels of MMP-10 and TIMP-1, higher MMP-10/TIMP-1 ratios, and lower MMP-9/TIMP-1 ratios than did healthy controls (P < 0.001). An association was found between MMP-9, MMP-10, TIMP-1, and MMP-9/TIMP-1 ratios and parameters of sepsis severity, assessed by the SOFA score, the APACHE-II score, lactic acid, platelet count, and markers of coagulopathy. Nonsurviving sepsis patients had lower levels of MMP-9 (P = 0.037), higher levels of TIMP-1 (P < 0.001), lower MMP-9/TIMP-1 ratio (P = 0.003), higher levels of IL-10 (P < 0.001), and lower TNF-α/IL-10 ratio than did surviving patients. An association was found between MMP-9, MMP-10, and TIMP-1 levels, and TNF-α and IL-10 levels. The risk of death in sepsis patients with TIMP-1 values greater than 531 ng/ml was 80% higher than that in patients with lower values (RR = 1.80; 95% CI = 1.13 to 2.87;P = 0.01; sensitivity = 0.73; specificity = 0.45). The novel findings of our study on patients with severe sepsis (to our knowledge, the largest series reporting data about MMP levels in sepsis) are that reduced MMP-9/TIMP-1 ratios and increased MMP-10 levels may be of great pathophysiologic significance in terms of severity and mortality, and that TIMP-1 levels may represent a biomarker to predict the clinical outcome of patients with sepsis.
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影响因子：
2.1
作者：
Albert, J;Radomski, A;Radomski, MW
通讯作者：
Radomski, MW
影响因子：
5
作者：
Lee, Ye-Ming;Lee, Jie-Jen;Sheu, Joen-Rong
通讯作者：
Sheu, Joen-Rong
DOI：
10.1186/cc2459
发表时间：
2004-04
期刊：
Critical care (London, England)
影响因子：
--
作者：
Kinasewitz GT;Yan SB;Basson B;Comp P;Russell JA;Cariou A;Um SL;Utterback B;Laterre PF;Dhainaut JF;PROWESS Sepsis Study Group
通讯作者：
PROWESS Sepsis Study Group
影响因子：
3.1
作者：
Kassim, Sean Y.;Gharib, Sina A.;McGuire, John K.
通讯作者：
McGuire, John K.
影响因子：
64.8
作者：
BRENNER, DA;OHARA, M;KARIN, M
通讯作者：
KARIN, M