期刊
SHOCK
卷 19, 期 5, 页码 462-468出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/01.shk.0000055240.25446.16
关键词
heme oxygenase-1; distal organ injury; oxidative stress; lung injury; intestinal ischemia
Intestinal ischemia/reperfusion (I/R) is a critical and triggering event in the development of distal organ dysfunction, frequently involving the lungs. Respiratory failure is a common cause of death and complications after intestinal I/R. Stress protein heme oxygenase-1 (HO-1) confers the protection against a variety of oxidant-induced cell and tissue injuries. The aim of this study was to investigate the hypothesis that the induced HO-1 expression by pharmacological preconditioning with anticancer drug doxorubicin (Dox) could protect the lung injury induced by intestinal I/R. Intravenous administration of Dox induced HO-1 expression in the lungs and high levels of the expression were sustained at least to 48 h after the injection. Therefore, as pharmacological preconditioning, a low dose of Dox was injected intravenously into rats at 48 h before the start of intestinal ischemia. Rats underwent intestinal I/R by superior mesenteric artery occlusion for 120 min followed by 120 min of reperfusion. Preconditioning with Dox significantly ameliorated the lung injury induced by the intestinal I/R. Administration of a specific inhibitor of HO activity reduced the efficacy of the preconditioning. Our results suggest that this improvement may be mediated at least in part by the HO-1 induction. These findings may offer interesting perspectives for patient management in intestinal surgical operation and intestine transplantation.
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