The Expression Of Hypoxia-inducible Factor-1alpha And Inducible Nitric Oxide Synthase In Inflammatory Bowel Disease

Objective: This study was to immunolocalize and assess the quantity of hypoxia-inducible factor-lalpha and inducible nitric oxide synthase in human normal colon mucosa and inflammatory bowel disease. on this base, we would like to illustrate and assess the potential roles of HIF-1α and iNOS in the pathophysiological function of inflammatory bowel disease and its mechanism.Methods: Paraffin was embedded tissues from inflammatory bowel disease which was diagnosed by clinical, endoscopic, histological and radiological criteria, the apparently normal colonic sections were obtained from pations treated for colon malignant disease by surgical. The 70 samples include 10 normal colonic sections, 47 ulcerative colitis cases, 13 Crohn's disease cases (three groups). The Streptaridin-Peroxidase Coiugated Method (SP Method) was employed to immunostain and to elucidate the localization and distribution of HIF-1α and iNOS.Results: The immunoreactivity was demonstrated in the cells as following: (1) HIF-1α expressing cells were scarcely found in normal colonic tissues,but HIF-1α was strongly expressed unequivocally in ulcerative colitis and Crohn's disease, the pattern of immunostaining of HIF-1α expression was confined to the surface and glandular epithelial cells, endothelial cells, stromal fibroblasis, inflammatory cells (macrophages and lymphocytes), being cytoplasmic and/or nuclear. The Median of positive rate of HIF-1α expression was 1.14%,54.39%,58.95% in 10 normal colon mucosa, 47 ulcerative colitis, 13 Crohn's disease respectively. The marked difference of HIF-1α was seen between ulcerative colitis and normal colon mucosa, and the same as between Crohn's disease and normal colon mucosa(.P<0.01), but the no difference was detected between ulcerative colitis and Crohn's disease(P>0.05). The expression level of HIF-1α in IBD was not closely related to age and sex(P>0.05). (2)The iNOS expression in normal colonic tissues showed no staining, but iNOS was strongly expressed in ulcerative colitis and Crohn's disease, the pattern of immunostaining of iNOS expression was confined to the epithelial cells, endothelial cells, stromalfibroblasis, inflammatory cells (macrophages and lymphocytes), being cytoplasmic. The Median of positive rate of iNOS expression was 2.14%,58.12%,54.29% in three groups respectively. The marked difference of iNOS was seen between ulcerative colitis and normal colon mucosa, and the same as between Crohn's disease and normal colon mucosa(P<0.01), but the no difference was detected between ulcerative colitis and Crohn's disease(P>0.05). The expression level of iNOS in IBD was not closely related to age and sex(/^>0.05).(3) The correlation between HIF-1 a and iNOS was embodyed in ulcerative colitis and Crohn's disease, linear correlation analysis showed that iNOS was positively correlated with HIF-1 a (ulcerative colitis: r=0.627; Crohn's disease: r=0.6\QJP<0.05).Conclusions: (1) HIF-1 a and iNOS were regularly expressing in inflammatory bowel diseases, and the two factors may be played an important pathophysiological function in inflammatory bowel disease; (2) There may be a significantly hypoxia condition and a possible mechanism for hypoxia preconditioning; (3) HIF-1 a may be one of the essential regulators of iNOS gene expression.