基质金属蛋白酶抑制剂对肺缺血再灌注损伤的保护作用

Protective Effect of Matrix Metalloproteinase Inhibitor on Lung Ischemia-reperfusion Injury

目的研究外源性基质金属蛋白酶(matrix metalloproteinases,MMPs)抑制剂强力霉素在肺缺血再灌注损伤中的保护作用。方法建立大鼠肺缺血再灌注模型,通过明胶酶谱法测定肺泡灌洗液(BAL)中明胶酶即MMP-2、MMP-9活性,免疫组化法测定肺组织中MMP-2、MMP-9的分布及含量,考马斯亮蓝比色法测定BAL中总蛋白的含量,测定肺组织湿干重比值,观察肺组织病理学改变。结果肺缺血再灌注后,MMP-2、MMP-9分泌及激活有显著提高,应用强力霉素30 mg/(kg.d)后,MMP-2、MMP-9分泌及激活被显著抑制,BAL中总蛋白含量显著降低,肺组织的病理改变显著减轻。结论强力霉素通过抑制明胶酶的分泌及激活,降低基底膜的降解,减轻肺水肿,达到肺保护作用。

Objective To investigate the protective effeets of exogenous matrix metalloproteinase inhibitor on lung ischemia-reperfusion injury. Methods The models of lung ischemia-reperfusion injury in SD rats were developed were measured. The activity of MMP-2 and MMP-9 in the bronchoalveolar lavage fluid （BAL） and the distribution and content in lung tissues by using zymography and immunohistochemical assays respectively. The total protein of BAL was determined by using Coomassie bulliant blue colormetricto, and wet/dry ratio was measured and pathological changes of lung tissue observed. Results The content and activity of MMP-2 and MMP-9 were significantly increased after lung ischemia-reperfusion injury, but decreased when 30 mg/（kg·d） doxycycline was used. Accordingly, the BAL total protein and wet/dry ratio were reduced and the histological changes in the lung tissues alleviated significantly. Conclusion Doxycycline can inhibit the secretion of MMPs and prevent activation of pro-MMPs to MMPs, sequentially, attenuate basement membrane degradation and lung edema to protect lung from ischemia-reperfusion injury.