The Correlation Between Mucosal Healing And Anemia In Inflammatory Bowel Disease And The Impact Of Iron On Intestinal Epithelial Cells

Background:Inflammatory bowel disease is a chronic,non-specific intestinal inflammatory disease with unclear etiology.Anemia is one of the common parenteral manifestations of inflammatory bowel disease,which can lead to decreased quality of life,decreased work capacity,and increased hospitalization rates.Clinical disease activity index and serological inflammation biomarkers can not accurately reflect the severity of intestinal inflammation in patients.And patients with clinical remission and serological remission may still have endoscopic active inflammation.Little is known about the relationship between anemia and endoscopic inflammation in patients with inflammatory bowel disease with clinical and serological remission.Oral iron supplementation is often used to treat inflammatory bowel disease with iron deficiency anemia.Studies have shown that oral iron supplementation may change the composition of the intestinal microbiome and increase the permeability of the intestinal epithelium in the treatment of inflammatory bowel disease with iron deficiency anemia.There are still few studies on the effects of iron on the function of intestinal epithelial cells.Aims:This thesis consists of two parts.The frrst part is clinical research.It aims to investigate the correlation between endoscopic mucosal healing and anemia in patients with inflammatory bowel disease who are in clinical remission and serological remission.The second part is aim to investigate the impacts of iron on intestinal epithelial cell function and ruechanisms in vivo and vitro experiments.Methods:In this retrospective study,113 patients with ulcerative colitis and 189 patients with Crohn's disease were included.Predictors of anemia were explored by logistic regression.A mice colitis model was established in vivo and cellular inflammatory model was constructed in vitro.Ferric iron agent was added for stimulation in botih vivo and vitro.The tight junctions,migration abilities,and changes in intracellular signaling pathways between intestinal epithelial cells were examined in this study.Results:1.Twenty-seven patients(23.9%)with ulcerative colitis and 72 patients(38.1%)with Crohn's disease were anemic.2.Female sex was an independent predictor of anemia in both ulcerative colitis odds ratio(OR),5.11;P=0.001]and Crohn's disease(OR,4.62;P<0.001).Ileocolonoscopy identified mucosal healing was an independent protective factor for anemia in ulcerative colitis(OR,0.32;P=0.028)but not in Crohn's disease.Normal pan-intestinal mucosa identified by ileocolonoscopy and capsule endoscopy was an independent protective factor for anemia in Crohn's disease(OR,0.15;P=0.001).3.At 1-year follow-up,the median hemoglobin concentration increased from 134g/L to 143g/L(P=0.001)in patients with ulcerative colitis achieving ileocolonoscopy identified mucosal healing and increased from 136g/L to 148g/L(P=0.001)in patients with Crohn's disease achieving normal pan-intestinal mucosa.4.In mouse colitis model,the mice were stimulated with iron through intragastric administration,The weight of the mice decreased significantly,the mortality increased.Intestinal epithelial cells of the mice were severely damaged,and a large number of inflammatory cells infiltrated,and the expression of tight junction proteins in the intestinal epithelial cells of the mice decreased significantly.5.In cell inflammatory model established in vitro,tight junction protein and migration ability discreased due to the stimulation of iron supplement.Iron supplement induced cell cycle to get arrested.6.Iron might have an influence on epithelial cells through AKT/mTOR pathway.Conclusions:Endoscopic inflammation was associated with anemia in patients with inflammatory bowel disease with clinical and serological remission.Adequate treatment of endoscopic inflammation may help to normalize hemoglobin concentration.When patients with inflammatory bowel disease need iron supplementation,intravenous iron supplementation may be considered to avoid damage to intestinal epitihelial cells by oral iron supplementation.