MMP-2 and MMP-9 and their tissue inhibitors in the plasma of preterm and term neonates
MMP-2 and MMP-9 and their tissue inhibitors in the plasma of preterm and term neonates
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DOI：
10.1203/01.pdr.0000120683.68630.fb
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发表时间：
2004-05-01
影响因子：
3.6
通讯作者：
Cheung, PY
中科院分区：
文献类型：
--
作者：
Schulz, CG;Sawicki, G;Cheung, PY
基质金属蛋白酶（MMP）及其组织抑制剂（TIMP）参与多种生理生长和发育以及病理生理炎症状况。我们假设 1) 早产儿和足月新生儿的 MMP-2 和 -9 血浆活性以及 TIMP-1 和 -2 血浆浓度取决于孕龄和产后年龄； 2) 早产儿支气管肺发育不良 (BPD) 和脑室内出血 (IVH) 的发展过程中，相应的 MMP 及其抑制剂发生紊乱。从1998年到1999年，从患有或不患有BPD和/或IVH的早产新生儿（妊娠25-36周）以及生命前28天的健康足月（妊娠37-40周）新生儿采集血液样本。通过酶谱法测量 MMP-2 和 MMP-9 血浆活性；通过ELISA测定TIMP-1和TIMP-2血浆浓度。在没有 BPD 或 IVH 的新生儿 (n = 50) 中，MMP-2 和 MMP-9 血浆活性似乎均与孕龄相关，在妊娠 33-36 周的新生儿中观察到最高水平。 TIMP-1 血浆浓度在足月新生儿中最高，但 TIMP-2 没有发现妊娠差异。仅 MMP-9 在产后第 1 个月第 1 天后显示出 50% 的下降。 12 名患有 BPD 和/或 IVH 的早产儿与不患有 BPD 或 IVH 的相应新生儿相比，其 MMP-2 显着较低，但 MMP-9 活性较高，TIMP-1 浓度较高。这些发现显示血浆 MMP 活性及其抑制剂的孕龄依赖性表达。 MMP 和 TIMP 可能参与胎儿新生儿发育，并可能导致危重早产新生儿 BPD 和/或 IVH 的发病机制。
Matrix metalloproteinases (MMP) and their tissue inhibitors (TIMP) are involved in a variety of physiologic growth and development and pathophysiologic inflammatory conditions. We hypothesized that 1) MMP-2 and -9 plasma activities and TIMP-1 and -2 plasma concentrations in preterm and term neonates were dependent on the gestational and postnatal age; and 2) the respective MMP and their inhibitors were deranged in the development of bronchopulmonary dysplasia (BPD) and intraventricular hemorrhage (IVH) in preterm neonates. From 1998 to 1999, blood samples were collected from preterm neonates (25-36 wk gestation) with or without BPD and/or IVH as well as from healthy term (37-40 wk gestation) neonates during the first 28 d of life. MMP-2 and MMP-9 plasma activities were measured by zymography; TIMP-1 and TIMP-2 plasma concentrations were determined by ELISA. In neonates without BPD or IVH (n = 50), MMP-2 and MMP-9 plasma activities both appeared to be gestational age dependent, with the highest levels observed in neonates of 33-36 wk gestation. TIMP-1 plasma concentration was highest in term neonates but no gestational difference was found in TIMP-2. Only MMP-9 showed a 50% decrease after d 1 in the first postnatal month. Twelve preterm infants with BPD and/or IVH had significantly lower MMP-2 but higher MMP-9 activity and higher TIMP-1 concentration than those of corresponding neonates without BPD or IVH. These findings show the gestational age-dependent expression of plasma MMP activities and their inhibitors. MMP and TIMP may be involved in the feto-neonatal development and may contribute to the pathogenesis of BPD and/or IVH in critically ill preterm neonates.