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Study On The Effect And Mechanism Of Enteral Nutrition On Colitis

Posted on:2019-04-25Degree:DoctorType:Dissertation
Country:ChinaCandidate:T YuFull Text:PDF
GTID:1364330572462336Subject:Clinical medicine internal medicine digestive system disease
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Inflammatory bowel disease is a kind of chronic intestinal nonspecific inflammation mainly located in colon and rectum,which has the characteristics of chronic delay and recurrent attack.Inflammatory bowel disease mainly includes ulcerative colitis and Crohn's disease.Ulcerative colitis mainly occurs in the colon tissue,whose effects have resulted in severe impairment of the physiological function of the colon tissue.Crohn's disease occurs throughout the digestive tract and is a systemic inflammatory disease.When intestinal epithelial barrier function is destroyed,it will cause intestinal microbial displacement,into the colon tissue,and then cause the immune cells to raise and excessive activation,and eventually develop into chronic inflammation,destroy normal tissue.At present,inflammatory bowel disease is related to many factors,such as heredity,environment,microorganism and immunity,but the exact pathogenesis is still unknown.Enteral nutrition was achieved in the clinical application,which not only provided sufficient nutrients for the body,but also improved the prognosis of critically patients played a combined role of nutrition and pharmacology.In this study,we mainly investigated the influence of enteral nutrition on inflammatory bowel disease and elucidated its molecular mechanism.In the first chapter,we investigated the effect of enteral nutrition on DSS induced colitis in mice.The anti-inflammatory activity of enteral nutrition was studied by establishing DSS model.Research shows that enteral nutrition improved DSS-induced colitis in mice,including weight loss,colon length shortened,watery and bloody stool.Enteral nutrition also inhibited the secretion of cytokines in serumand colon tissues of DSS mice.Pathological analysis of H&E staining of colonic tissue showed that enteral nutrition could reduce the pathological damage in mice with colitis.By detecting the expression of inflammatory cell surface antigen CD11 b,it was found that enteral nutrition could inhibit the infiltration of inflammatory cells in colon lesions.Intestinal inflammation activated the activity of MPO and iNOS abnormally.The study found that enteral nutrition inhibited the abnormal activation of MPO and iNOS in colon tissue of mice.These results suggest that enteral nutrition can inhibit DSS-induced colitis in mice.In the second chapter,the effect of enteral nutrition on TNBS-induced colitis in rats was further investigated.By establishing the TNBS model,we found that enteral nutrition also improved the signs of TNBS-induced colitis in rats.The histopathological analysis showed that enteral nutrition reduced the pathological damage of colon tissue.In addition,enteral nutrition has been shown to inhibit MPO and iNOS activity in colon tissue.Enteral nutrition also inhibited the secretion of cytokines in serum and colon tissues of TNBS rats.These results suggest that enteral nutrition can inhibit TNBS-induced colitis in rats.In the progression of inflammatory bowel disease,abnormal activation of immune cells is a significant factor in the pathogenesis of colonic lesions.In order to investigate the possible mechanism of enteral nutrition for relieving colitis,the effect of enteral nutrition on peritoneal macrophages of DSS model was investigated.It was found that enteral nutrition inhibited the phosphorylation of NF-?B at Ser 276 sites in peritoneal macrophages.Further studies have shown that enteral nutrition inhibited the activation of NF-?B by regulating the p38/MSK1 signaling pathway.To confirm this conclusion,the activation of NF-?B in colon tissue of DSS model and TNBS model was investigated respectively.Studies have shown that in the colon tissue,enteral nutrition also inhibited the activation of NF-?B by regulating the p38/MSK1 signaling pathway.These results suggest that enteral nutrition inhibits the activation of NF-?B by regulating the p38/MSK1 signaling pathway and ultimately acts as an inhibitor of inflammatory bowel disease.In conclusion,this study investigated the role and molecular mechanism of enteral nutrition in inflammatory bowel disease.It is confirmed that enteral nutrition suppressed inflammatory bowel disease by inhibiting activation of NF-?B via regulating the p38/MSK1 signaling pathway.These findings are of guiding significance for the clinical application of enteral nutrition.
Keywords/Search Tags:enteral nutrition, inflammatory bowel disease, colitis, NF-?B, p38/MSK1 signaling pathways
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