Role of CO-releasing molecule in the lung injuried by limb ischemia-reperfusion

Objective To observe the role and mechanism of CO-releasing molecules （CORMs） -2 in the injured lung induced by ischmia-reperfusion （IR） of hind limbs of rat. Methods The rat model of lung injury was made by ischemia in hind limbs of rat for two hours and then reperfusion for two hours as well. There were 40 SD rats randomly （ random number） divided into 5 groups （ n = 8 ）, namely sham ischemia-reperfusion （I/R） group, sham I/R ＋ CORM-2 group, I/R group, I/R ＋ CORM-2 group and I/R ＋ DMSO （Dimethylsulfoxide） group. Rats in sham I/R group underwent laparotomy without infrarenal aorta occlusion. The lung tissue structure, polymorphonuclear neutrophil （PMN） count, wet-to-dry weight ratio （W/D）, malondialdehyde （MDA） content, myeloperoxidase （MPO） activity, intercellular adhesion molecule-1 （ICAM-1）, nuclear IKBcdegradation and NF-KB activity in the lung were measured. Results Compared with the sham I/R group, the number of PMNs in lung, W/D, MDA content, MPO activity, ICAM-1 and NF-KB activity significantly increased in I/R group, whereas nuclear IKBc~ decreased （P 〈0. 01）. Compared with the I/R group, the number of PMNs in lung, W/D, MDA content, MPO activity and ICAM-1 significantly decreased in I/R ＋ COMR-2 group （ P 〈 0. 01 ）, while nuclear IKBcdncreased. Conclusions These data demonstrate that CORM-2 attenuates limb I/R-induced lung injury by inhibiting ICAM-1 protein, NF-KB pathway and the leukocytes sequestration in the lung following limb I/R in rats, suggesting that CORM-2 could be used as one of the most valuable therapeutic agents. Key words: Carbon monoxide-releasing molecules ;  Lung ;  Reperfusion injury ;  Adhesion molecule ; Auclear factor kappa B