Effects of curcumin on MMP-9/TIMP-1 balance during limb ischemia-reperfusion-induced lung injury in rats

Objective To evaluate the effects of curcumin on matrix metalloproteinase-9 (MMP-9)/tissure inhibitor of metalloproteinase-1 (TIMP-1) balance during limb ischemia-reperfusion (I/R)-induced lung injury in rats.Methods Twenty-four adult male Sprague-Dawley rats,aged 6-8 months,weighing 250-300 g,were randomly divided into 3 groups (n =8 each) using a random number table:sham operation group (group S) ; group I/R; curcumin + I/R group (group C + I/R).Limb ischemia was induced by occlusion of bilateral femoral arteries for 2 h followed by reperfusion for 3 h in I/R and C + I/R groups.At 2 h before ischemia,curcumin 200 mg/kg was injected intraperitoneally in group C + I/R,while the equal volume of normal saline was given instead in the other groups.Arterial blood samples were taken at 3 h of reperfusion for blood gas analysis and PaO2 was recorded.The animals were then sacrificed and the lungs were removed immediately for determination of wet/dry lung weight (W/D) ratio,myeloperoxidase (MPO) activity and MMP-9 and TIMP-1 contents.The ratio of MMP-9/ TIMP-1 was calculated.Results Compared with group S,PaO2 was significantly decreased,and W/D ratio,MPO activity,MMP-9 content and the ratio of MMP-9/TIMP-1 were significantly increased (P ＜ 0.05),while no significant change was found in TIMP-1 content in group I/R (P ＞ 0.05).Compared with group I/R,PaO2 and TIMP-1 content were significantly increased,and W/D ratio,MPO activity,MMP-9 content and the ratio of MMP-9/TIMP-1 were significantly decreased in group C + I/R (P ＜ 0.05).Conclusion The mechanism by which curcumin attenuates lung injury induced by limb I/R is related to decreased MMP-9 content,elevated TIMP-1 content and regulated balance between MMP-9 and TIMP-1 in the lung tissues of rats. Key words: Curcumin;  Extremities;  Reperfusion injury;  Respiratory distress syndrome,adult;  Matrix metalloproteinase 9;  Tissue inhibitor of metalloproteinase-1