Ventilator-induced lung injury upregulates and activates gelatinases and EMMPRIN - Attenuation by the synthetic matrix metalloproteinase inhibitor, Prinomastat (AG3340)
Ventilator-induced lung injury upregulates and activates gelatinases and EMMPRIN - Attenuation by the synthetic matrix metalloproteinase inhibitor, Prinomastat (AG3340)
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DOI：
10.1165/ajrcmb.25.6.4558f
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发表时间：
2001-12-01
影响因子：
6.4
通讯作者：
Zucker, S
中科院分区：
文献类型：
--
作者：
Foda, HD;Rollo, EE;Zucker, S
机械通气已成为呼吸衰竭患者不可缺少的治疗手段。然而，机械通气的一个严重的潜在并发症是新近发现的呼吸机诱导的急性肺损伤。有强有力的证据表明，基质金属蛋白酶(MMPs)在急性肺损伤的发生发展中起重要作用。另一个要考虑的因素是细胞外基质金属蛋白酶诱导物(EMMPRIN)。EMMPRIN负责诱导成纤维细胞产生/分泌MMPs。在这份报告中，我们试图确定：(1)MMPs和EMMPRIN在大容量机械通气大鼠体内呼吸机诱导肺损伤(VILI)的发生中所起的作用；以及(2)合成的基质金属蛋白酶抑制剂PROMASAT(AG3340)是否可以预防这种类型的肺损伤。我们已经证明，大容量的通气会导致急性肺损伤。原位杂交显示，伴随着明胶酶A、明胶酶B、MT1-MMPs和EMMPRIN基因的表达上调。给予基质金属蛋白酶抑制剂普林司马特可减轻大容量通气量所致的肺损伤。我们的结果表明，MMPs在大鼠肺VILI的发生发展过程中起着重要作用，并且MMPs抑制剂普林司马特能有效地减轻这种类型的肺损伤。
Mechanical ventilation has become an indispensable therapeutic modality for patients with respiratory failure. However, a serious potential complication of MV is the newly recognized ventilator-induced acute lung injury. There is strong evidence suggesting that matrix metalloproteinases (MMPs) play an important role in the development of acute lung injury. Another factor to be considered is extracellular matrix metalloproteinase inducer (EMMPRIN). EMMPRIN is responsible for inducing fibroblasts to produce/secrete MMPs. In this report we sought to determine: (1) the role played by MMPs and EMMPRIN in the development of ventilator-induced lung injury (VILI) in an in vivo rat model of high volume ventilation; and (2) whether the synthetic MMP inhibitor Prinomastat (AG3340) could prevent this type of lung injury. We have demonstrated that high volume ventilation caused acute lung injury. This was accompanied by an upregulation of gelatinase A, gelatinase B, MT1-MMP, and EMMPRIN mRNA demonstrated by in situ hybridization. Pretreatment with the MMP inhibitor Prinomastat attenuated the lung injury caused by high volume ventilation. Our results suggest that MMPs play an important role in the development of VILI in rat lungs and that the MMP-inhibitor Prinomastat is effective in attenuating this type of lung injury.