Protection of carbon monoxide-releasing molecule against lung injury induced by limb ischemia-reperfusion / 中华创伤杂志(英文版)

ABSTRACT

<p><b>OBJECTIVE</b>To observe the role and mechanism of CO-releasing molecule (CORM)-2 in lung injury induced by ischemia-reperfusion (IR) of hind limbs in rats.</p><p><b>METHODS</b>A rat model of lung injury induced by IR of hind limbs was established. A total of 40 Sprague Dawley (SD) rats were randomly divided into 5 groups (n equal to 8): sham, sham + CORM-2, IR, IR + CORM-2 and IR + dimethyl sulfoxide (DMSO). Rats in the IR group received hind limb ischemia for 2 hours and reperfusion for 2 hours, rats in the sham group underwent sham surgery without infrarenal aorta occlusion, rats in the IR+CORM-2 group and in the sham + CORM-2 group were given CORM-2 (10 micromol/kg intravenous bolus) 5 minutes before reperfusion or at the corresponding time points, while rats in the IR + DMSO group was treated with the same dose of vehicle (DMSO) at the same time. 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) expression,IkBa degradation and nuclear factor (NF)-kB activity in the lungs were assessed.</p><p><b>RESULTS</b>As compared with the sham group, lung PMNs number, W/D, MDA content, MPO activity, ICAM-1 expression and NF-kB activity significantly increased in the IR group, but the level of IkBa decresed (P less than 0.01). Compared with the IR group, lung PMNs number, W/D, MDA content, MPO activity and ICAM-1 expression significantly decreased in the IR+COMR-2 group (P less than 0.01), while the level of IkBa increased.</p><p><b>CONCLUSIONS</b>These data demonstrate that CORM-2 attenuates limb IR-induced lung injury through inhibiting ICAM-1 protein expression, NF-kB pathway and the leukocytes sequestration in the lungs following limb IR in rats, suggesting that CORM-2 may be used as a therapeutic agent against lung injury induced by limb IR.</p>