Protective effects of superoxide dismutase against ischemia-reperfusion injury: development and application of a transgenic animal model.
Reperfusion of ischemic tissues can be associated with structural and functional injury, which is referred to as ischemia-reperfusion injury. Superoxide dismutase is an endogenous free radical scavenger that converts toxic oxygen derived free radicals to hydrogen peroxide. With the development of gene cloning technology, the potential of manipulating cells to overexpress endogenous proteins has been realized. Transgenic mice capable of overexpressing superoxide dismutase, and knockout mice in which the gene responsible for its production has been deleted, were used as a model to examine the protective effects of superoxide dismutase against ischemia-reperfusion injury. Epigastric island flaps were elevated in wild-type (control), transgenic superoxide dismutase 1, and knockout superoxide dismutase 1 mice and subjected to ischemic intervals of 0, 3, 6, 9, or 12 hours. Five animals were studied at each time point in each study group. Flap viability was assessed on postoperative day 7. Baseline wild-type flap survival was 100 percent after 3 hours of ischemia and subsequent reperfusion; survival decreased to 21 percent after 9 hours of ischemia. Transgenic mice had significantly higher flap survival than wild-type animals after 6 hours of ischemia and subsequent reperfusion (97.0 versus 85.2 percent) and after 9 hours of ischemia (82 versus 21 percent, p < 0.01). In knockout mice, there was complete flap necrosis after as little as 3 hours of ischemia. This study confirms the protective effects of superoxide dismutase against ischemia-reperfusion injury. In addition, its deficiency results in a dramatic susceptibility to ischemic injury.
Klein
Matthew B
MB
Division of Plastic Surgery, the Department of Neuroscience, Stanford University Medical Center, Calif 94022, USA.
Chan
Pak H
PH
Chang
James
J
D034861:Abdominal Wall / Q000601:surgery; D000818:Animals; D004195:Disease Models, Animal; D006085:Graft Survival; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D015427:Reperfusion Injury / Q000503:physiopathology* / Q000517:prevention & control; D013482:Superoxide Dismutase / Q000502:physiology*; D013524:Surgical Flaps / Q000098:blood supply*
D013482:Superoxide Dismutase