基质金属蛋白酶抑制剂对肺缺血再灌注损伤炎性反应的影响

Effects of matrix metalloproteinase inhibitor on the inflammation of the lung following ischemia-reperfusion injury

目的:探讨外源性基质金属蛋白酶(matrix metalloproteinase,MMPs)抑制剂强力霉素对肺缺血再灌注损伤炎性反应的影响。方法:建立大鼠肺缺血再灌注模型,测定肺泡灌洗液(bronchoalveolar lavage,BAL)中明胶酶即MMP-2、MMP-9活性,白细胞计数(WBC);肺组织中MMP-2、MMP-9分布及含量,肿瘤坏死因子-α(TNF-α),超氧化物歧化酶(SOD),丙二醛(MDA)含量及病理学改变。结果:肺缺血再灌注后,MMP-2、MMP-9分泌及活性显著提高,BAL中WBC、肺组织TNF-α、MDA显著升高;应用强力霉素后,MMP-2、MMP-9分泌及活性有显著抑制,BAL中WBC、肺组织TNF-α含量显著降低,肺组织病理改变显著减轻。结论:肺缺血再灌注损伤实质是一种炎症损伤,强力霉素主要通过抑制MMPs的分泌及激活,减轻肺缺血再灌注损伤炎性反应程度,达到肺保护作用。

Objective：To explore the effects of exogenous matrix metalloproteinase inhibitor on the inflammation of the lung following ischemia-reperfusion injury. Method： Models of ischemia-reperfusion lung injury in Sprague-Dawley （SD） rats were developed. The activity of MMP-2, MMP-9 and the white cell counting in the bronchoalveolar lavage fluid （BAL） were measured, the distribution and content of MMP-2, MMP-9 and TNF-α,SOD, MDA in lung tissue were determined, and the pathological change of lung tissue was observed. Result;The content and activity of MMP-2, MMP-9 significantly increased following ischemia-reperfusion lung injury but decreased when doxycycline was used. Accordingly, the white cell counting of BAL and the TNF-α of lung tissue lowered and the histological changes in the lung tissue alleviated significantly. Conclusion：Ischemia-reperfusion lung injury was due to the inflammation of lung . Doxycycline could inhibit the secretion of MMPs and prevent activation of pro-MMPs to MMPs, sequentially, attenuate the inflammation of lung and protect lung from ischemia-reperfusion injury.