Kinetics and Role of Plasma Matrix Metalloproteinase-9 Expression in Acute Lung Injury and the Acute Respiratory Distress Syndrome.
Kinetics and Role of Plasma Matrix Metalloproteinase-9 Expression in Acute Lung Injury and the Acute Respiratory Distress Syndrome.
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DOI：
10.1097/shk.0000000000000386
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发表时间：
2015-08
期刊：
影响因子：
--
通讯作者：
Yaffe MB
中科院分区：
文献类型：
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作者：
Hsu AT;Barrett CD;DeBusk GM;Ellson CD;Gautam S;Talmor DS;Gallagher DC;Yaffe MB
能够释放基质金属蛋白酶（MMPs）进入循环的致敏中性粒细胞被认为在急性呼吸窘迫综合征（ARDS）的病理生理学中起重要作用。我们假设直接测量血浆MMP-9活性可能是早期组织损伤和随后肺损伤的预测因子，这在ARDS动物模型和38例危重患者的小队列中进行了研究。在气管内滴注LPS诱导肺部炎症的ARDS小鼠模型中，我们测量了嗜中性粒细胞介导的炎症，以及气道和肺组织中MMP-9活性和血浆中MMP-9表达的沿着。在LPS滴注后72小时，气道和肺组织中的神经元募集、炎症和MMP-9活性增加，而血浆MMP-9表达在LPS滴注后12-24小时最大。结果提示，在ARDS发病过程中，血浆MMP-9活性的高峰可能先于气道和肺组织中性粒细胞炎症的高峰。基于该动物研究，进行了一项回顾性观察性队列研究，涉及38例在三级护理大学医院外科重症监护室（SICU）住院的急性呼吸衰竭患者，需要插管和机械通气。每天采集血浆样本，并将MMP-9活性与PaO 2/FiO 2比值测定的肺功能进行比较。在发生ARDS的患者中，特定日期血浆MMP-9活性显著升高与次日PaO 2/FiO 2比值降低相关（r =-0.503，p < 0.006）。总之，这些结果表明，血浆MMP-9活性的变化作为替代致敏的中性粒细胞可能有预测价值的发展ARDS在选定的子集的危重病人。
Primed neutrophils that are capable of releasing matrix metalloproteinases (MMPs) into the circulation are thought to play a significant role in the pathophysiology of acute respiratory distress syndrome (ARDS). We hypothesized that direct measurement of plasma MMP-9 activity may be a predictor of incipient tissue damage and subsequent lung injury, which was investigated in both an animal model of ARDS and a small cohort of 38 critically ill human patients. In a mouse model of ARDS involving instillation of intratracheal LPS to induce lung inflammation, we measured neutrophil-mediated inflammation, along with MMP-9 activity in the airways and lung tissue and MMP-9 expression in the plasma. Neutrophil recruitment, inflammation, and MMP-9 activity in the airways and lung tissue increased throughout the 72 hours after LPS instillation, while plasma MMP-9 expression was greatest at 12–24 hours after LPS instillation. The results suggest that the peak in plasma MMP-9 activity may precede the peak of neutrophil inflammation in the airways and lung tissue in the setting of ARDS. Based on this animal study, a retrospective observational cohort study involving 38 patients admitted to a surgical intensive care unit (SICU) at a tertiary care university hospital with acute respiratory failure requiring intubation and mechanical ventilation was conducted. Plasma samples were collected daily, and MMP-9 activity was compared with lung function as determined by the PaO2/FiO2 ratio. In patients that developed ARDS, a notable increase in plasma MMP-9 activity on a particular day correlated with a decrease in the PaO2/FiO2 ratio on the following day (r = −0.503, p < 0.006). Taken together, these results suggest that plasma MMP-9 activity changes as a surrogate for primed neutrophils may have predictive value for the development of ARDS in a selected subset of critically ill patients.