Matrix metalloproteinases and TIMP in acute respiratory distress syndrome
Matrix metalloproteinases and TIMP in acute respiratory distress syndrome
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DOI：
10.1164/ajrccm.154.2.8756805
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发表时间：
1996-08-01
影响因子：
24.7
通讯作者：
Dayer, JM
中科院分区：
文献类型：
--
作者：
Ricou, B;Nicod, L;Dayer, JM
为探讨细胞外基质蛋白在急性呼吸窘迫综合征(ARDS)中的作用，对33例合并创伤或感染性休克的重症监护病房(ICU)患者支气管肺泡灌洗液(BALF)和血浆中92kD明胶酶(92G‘ase)及其天然拮抗剂金属蛋白酶组织抑制因子-1(TIMP)进行检测。这些患者中有11人发展为短程ARDS，9人发展为长期ARDS，13人没有进展为ARDS。10例非ICU患者作为对照。在疾病早期，ICU患者BALF中92G‘ase水平高于对照组，但血浆水平无明显差异。ARDS患者BALF和血浆中TIMP水平明显高于高危患者。BALF中92G‘ase/TIMP比值在延迟性ARDS晚期持续升高。高危和ARDS患者肺内高水平的92G‘ase可能反映了急性肺损伤时细胞外基质的周转增加。升高的TIMP可能通过抑制92G‘酶而干扰组织修复和纤维化。白介素6(IL-6)可能参与促进局部合成TIMP。92G‘ase和TIMP之间的平衡可能在ARDS所特有的肺重塑中起重要作用。
To investigate the implication of extracellular matrix proteinases in acute respiratory distress syndrome (ARDS), we determined 92 kD gelatinase (92 G'ase) and its natural antagonist, the tissue inhibitor of metalloproteinases-1 (TIMP) in bronchoalveolar lavage fluid (BALF) and plasma of 33 intensive care unit (ICU) patients presenting with trauma or septic shock. Eleven of these patients developed short-course ARDS, nine developed prolonged ARDS, and 13 did not progress to ARDS. Ten non-ICU patients served as controls. During the early phase of disease, 92 G'ase in BALF of ICU patients was higher than in controls, but plasma levels were not different. TIMP was increased in BALF and plasma in ARDS as compared with those of patients at risk. The 92 G'ase/TIMP ratio in BALF remained elevated in late phases of prolonged ARDS. The high intrapulmonary levels of 92 G'ase in patients at risk and with ARDS may reflect increased turnover of extracellular matrix in acute lung injury. Increased TIMP may interfere with tissue repair and fibrosis by its inhibition of 92 G'ase. Interleukin-6 (IL-6) could be involved in enhanced local synthesis of TIMP. The balance between 92 G'ase and TIMP may play an important role in lung remodeling, which is characteristic of ARDS.