Early endothelial damage and increased colonic vascular permeability in the development of experimental ulcerative colitis in rats and mice

摘要: The role of endothelial damage and increased vascular permeability (VP) in the pathogenesis ulcerative colitis (UC) has not been investigated. We examined using functional, morphologic, molecular biologic studies whether to what extent barrier dysfunction precedes enhanced epithelial (EP) development mucosal lesions during early stages experimental UC. showed that rats with iodoacetamide (IA)-induced UC colonic VP occurs (ie, 2.6-fold increase at 15 min, P<0.01) preceding changes permeability. EP was unchanged 30 min after IA administration 1.9-fold 1 h 6.7-fold 2 (both P<0.001) IA. In dextran sodium sulfate-induced slowly developing UC, significantly days (P<0.05) only 4 (P<0.05). Mucosal injury led hypoxia surface cells associated expressions transcription factors hypoxia-inducible factor-1α growth response-1. Electron light microscopy demonstrated areas mucosa perivascular edema covered by intact layer both rat mouse models This is first demonstration four damage, VP, edema, precede followed erosions, ulceration, inflammation