Expression of matrix metalloproteinases in pigs with hyperoxia-induced acute lung injury
Expression of matrix metalloproteinases in pigs with hyperoxia-induced acute lung injury
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DOI：
10.1183/09031936.01.00049201
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发表时间：
2001-11-01
影响因子：
24.3
通讯作者：
Ando, M
中科院分区：
文献类型：
--
作者：
Gushima, Y;Ichikado, K;Ando, M
本研究的目的是确定基质金属蛋白酶（MMMPs）在高氧急性肺损伤发病机制中的作用。将23头猪置于密闭笼中，暴露于> - 80%的氧气环境（24-120 h）或室内空气中，采用明胶酶谱法测定支气管肺泡灌洗液（BALF）中MMP-2/MMP-9活性的相关性，并详细检查组织学结果和病理参数。通过免疫组织化学分析高氧肺中这些MMPs的来源。该模型急性肺损伤的组织学进展范围从弥漫性肺泡损伤（DAD）的早期渗出期到早期增殖期。MMP-2和-9活性在长时间高氧暴露下升高。MMP-9活性与动脉血氧张力/吸气氧分数、肺干湿比is- 8和BALF中性粒细胞数量显著相关，而MMP-2活性与这些因素完全不相关。与MMP-2活性相比，MMP-9活性与DAD病理表现的相关性更密切。在中性粒细胞、肺泡巨噬细胞和肺泡上皮细胞中观察到强烈的MMP-9表达。这些结果表明，基质金属蛋白酶可能来源于招募到空气中的中性粒细胞，在高氧弥漫性肺泡损伤的发病机制中起重要作用。
The aim of this study was to determine the role of matrix metalloproteinases (MMMPs) in the pathogenesis of acute lung injury induced by hyperoxia.Twenty-three pigs were exposed in sealed cages to > 80% oxygen (for 24-120 h) or room air, Correlation between MMP-2/MMP-9 activity, measured by gelatin zymography in bronchoalveolar lavage fluid (BALF), and the histological findings and pathological parameters were examined in detail. Sources of these MMPs in the hyperoxic lung were analysed by immunohistochemistry..The histological progression of acute lung injury in this model ranged from the early exudative to the early proliferative phase of diffuse alveolar damage (DAD). MMP-2 and -9 activities were elevated under prolonged hyperoxic exposure. MMP-9 activity correlated significantly with the oxygen tension in arterial blood/inspiratory oxygen fraction, the lung wet-to-dry is-eight ratio, and the number of neutrophils in BALF, whereas MMP-2 activity did not correlate at all with these factors. MMP-9 activity correlated more closely with the pathological findings of DAD than did MMP-2 activity. Strong MMP-9 expression was observed in neutrophils, alveolar macrophages as well as alveolar lining epithelial cells.These results suggest that matrix metalloproteinase, which may derive from neutrophils recruited into airspaces, plays an important role in the pathogenesis of hyperoxic diffuse alveolar damage.