MECHANISMS OF REPAIR OF ISCHEMIC INJURED INTESTINE

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The goal of this laboratory is to identify mechanisms of intestinal repair in order to facilitate recovery of injured intestine. Intestinal ischemial reperfusion injury is of particular interest because of its role in the equine colic syndrome, the principal killer of horses. A model of ischemia/ reperfusion injury will be developed in the pig. It is possible that the pig will provide a better model for the human and the horse, because of similar low levels of xanthine oxidase. The relative contribution of ischemia and reperfusion to intestinal injury will be determined. Ischemic injury appears to he more important in large animal species than reperfusion injury, as opposed to rodent models in which reperfusion injury is prominent. Because of a failure to block reperfusion injury in the horse, and the questionable relevance of rodent models of reperfusion injury to the human, the repair process will be characterized. The ability of glutamine (GLN) and growth factors to enhance proliferation will be investigated, and the mechanism by which GLN facilitates repair will he examined. Specifically, activation of Jun-nuclear kinase and Mitogen-activated kinase, enzymes critical for the induction of "early- immediate" genes, will be assessed. These studies should provide basic information on mechanisms of epithelial proliferation and alternative therapeutic approaches to ischemic injury.