Low levels of tissue inhibitors of metalloproteinases with a high matrix metalloproteinase-9/tissue inhibitor of metalloproteinase-1 ratio are present in tracheal aspirate fluids of infants who develop chronic lung disease
Low levels of tissue inhibitors of metalloproteinases with a high matrix metalloproteinase-9/tissue inhibitor of metalloproteinase-1 ratio are present in tracheal aspirate fluids of infants who develop chronic lung disease
复制标题
DOI：
10.1542/peds.113.6.1709
复制
发表时间：
2004-06-01
期刊：
影响因子：
8
通讯作者：
Truog, WE
中科院分区：
文献类型：
--
作者：
Ekekezie, II;Thibeault, DW;Truog, WE
Objective.慢性肺疾病（CLD）的发病机制涉及炎症和肺细胞外基质的蛋白水解损伤。基质金属蛋白酶（MMP）是锌依赖性内肽酶，其与其组织抑制剂协同作用，紧密协调细胞外基质的形态发生和损伤后的修复。其水平相对于其抑制剂的水平的不平衡与以基质破坏和重塑为特征的疾病有关。我们研究了早产儿气管吸出物中MMP-9和MMP-2相对于其组织金属蛋白酶抑制剂-1（TIMP-1）和TIMP-2的失衡可能参与CLD的发展。对49例接受机械通气的早产儿（妊娠24-32周）从出生至拔管期间收集的连续气管抽吸物进行MMP-2、MMP-9、TIMP-1和TIMP-2分析。将CLD（n=22）与无CLD（n=27）的免疫球蛋白A游离分泌组分的TA值标准化的数据进行比较。此外，对两组已知的CLD临床预测因素（胎龄、出生体重和性别）进行了评估。通过逻辑回归分析评估CLD预后的预测因素。CLD婴儿的平均胎龄较低，但两组的出生体重和性别相当。与非CLD婴儿相比，CLD婴儿在出生后的前2周内TIMP-1水平显著降低，MMP-9/TIMP-1比值显著升高，在出生后的前3天内TIMP-2和MMP-2水平显著降低。Logistic回归分析表明，这些结果对慢性肝病有预测作用。我们的结论是，气管吸出物中TIMP水平低，生命早期MMP-9/TIMP-1比值高，与CLD的后续发展相关。
Objective. The pathogenesis of chronic lung disease (CLD) involves inflammation with proteolytic damage to lung extracellular matrix. Matrix metalloproteinases (MMPs) are zinc-dependent endopeptidases that, acting in concert with their tissue inhibitors, tightly orchestrate extracellular matrix morphogenesis and repair after injury. Imbalances in their levels relative to that of their inhibitors have been implicated in diseases characterized by matrix disruption and remodeling. We investigated the possibility that imbalances in MMP-9 and MMP-2 relative to their tissue inhibitor of metalloproteinase-1 (TIMP-1) and TIMP-2, respectively, in tracheal aspirates of preterm infants may be involved in the development of CLD.Methods. Serial tracheal aspirates collected from birth until extubation in 49 ventilated preterm infants (24-32 weeks' gestations) were analyzed for MMP-2, MMP-9, TIMP-1, and TIMP-2. Data normalized by TA values of free secretory component of immunoglobulin A were compared for CLD (n=22) versus no CLD (n=27). Also, known clinical predictors of CLD (gestational age, birth weight, and sex) were assessed for both groups. Association of predictors with the outcome CLD was assessed by logistic regression.Results. Mean gestational age was lower in CLD infants, but birth weight and gender were comparable for both groups. CLD infants had significantly lower TIMP-1 level with higher MMP-9/TIMP-1 ratio during the first 2 weeks of life and low TIMP-2 and MMP-2 levels during the first 3 days of life compared with no-CLD infants. Logistic regression analysis indicated that the findings are predictive of CLD.Conclusions. We conclude that low tracheal aspirate levels of TIMPs, with a high MMP-9/TIMP-1 ratio early in life, are associated with subsequent development of CLD.