Study Of The Pathogenesis And Drug Therapy Of Inflammatory Bowel Disease With An Immune Animal Model

Inflammatory bowel disease(IBD) which is grouped by two entities as Crohn's disease and ulcerative colitis, is a common alimentary disease that has a worldwide high incidence and demonstrates an increasing morbidity during the past decade in China. Till now,limited progress has occurred in the study of etiology and pathogenesis of IBD. And many problems still remain in its diagnosis and treatment. In the 70s through the 90s,the most common vehicles used by investigators to travel the scientific avenues of IBD have been immunology,genetics,and animal models.In this study, first of all,a rat model of chronic recurrent experimental colitis was established.It was induced firstly by rectal administration of the hapten 2,4,6-trinitro-benzenesulfonic acid (TNBS)30mg in 50% ethanol 0.25ml as the "barrier breaker". And then it recurred only after 10mg TNBS rectal administration alone,which could not induce colitis at the beginning.An acute inflammation with ulcers and neutrophil infiltration developed that evolved into a chronic inflammation with luminol narrowing and abundant fibrous connective tissue hypertrophy at 21 days. Crpt abcesses were observed in some rats killed in 3rd day and 1st week of colitis. And the acute pathologic characters above reappearred after colitis re-induced by 10mg TNBS giving alone. Inflammation was assessed by gross appearance using a grading scale and by histology. In order to evaluate the model more accurately,Myeloperoxidase(MPO) and Super- oxide Dismutase(SOD) activities were also measured to evaluate the severity of inflammation. MPO activity was significantly elevated,while SOD declined in mucosa from all TNBS/ethanol-treated groups at all time intervals when macroscopic and microscopic mucosal injury was evident. These results indicated that this modified TNBS/ethanol model could afford an opportunity to study the pathophysiology of colonic inflammatory disease and might be used to evaluate new treatments potentially applicable to inflammtory bowel disease in humans. In addition, MPO and SOD activities could be regarded as two markers which may evaluate the severity of colonic inflammation.On the basis of the established modified IBD model,we set about studying the action of cytokines(TL-l β and IL-8) on the pathogenesis of IBD and exploring some...