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Experimental Studies On Urinastatin In The Treatment Of Ulcerative Colitis

Posted on:2004-09-18Degree:MasterType:Thesis
Country:ChinaCandidate:Z J LiFull Text:PDF
GTID:2144360092499166Subject:Digestive science
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Background Ulcerative colitis(UC) is a common disease . In recent 10 years, with the development of molecular biology, the pathogenesis of UC has been investigated on the level of molecule by many scholars . It was found that many cytokines ,adhesion molecules, inflammatory mediums, oxygen radicals participate in the processes of UC. But it is difficult to treat UC, especially in some serious cases, for there is a complicated pathophysiological process influenced by multiple factors in UC, and the mechanisms is unclear. In addition, there is no effective measures to block its pathophysiological process directly.Recently many studies show that tumor necrosis factor-alpha (TNF-alpha), an pro- inflammatory and immune regulative cytokin plays an important role in pathophysiological process of UC. It is correlated with beginning, progress and prognosis in UC. P-selectin is a land of cell adhesion molecules. It plays important role in mediating leukocyte-endothelial interaction, immunologic rejection in organ transplantation, growing of tumor cells and vascularization. In recent years there are also researches showing that P-selectin and oxygen radicals play important role in UC. Oxygen radicals, as a kind of inflammatory mediators causes inflammatory lesion and increases tissue lesion in gastric and intestinal ischaemia reperfusion injury. But there is no systemic investigational study about altering regularity and roles in assessing inflammatory severity for TNF-alpha, P-selectin and oxygen radicals in UC.Ulinastatin is a kind of inhibitor of trypsin separated from health man's urine, which has two active functional regions. In clinic it has been used for the therapy of pancreatitis, shock, and resisting injury of surgeon, as well as implication of extracorporeal circulation. Recently it is convinced that ulinastatin can reduce inflammatory medium and oxygen radicals. But retrieving historical documents, we don't find any report about theadministration of ulinastatin in UC treatment.Objective l.By making a rat UC model and measuring the dynamic changes of TNF-alpha, P-selectin, malondialdehyde(MDA), superoxide dismutase(SOD) and colon mucosal ulceration index, we investigated the pathological mechanism and roles in assessing inflammatory severity in UC so as to provide preliminary experimental foundation for the clinical study.2. In order to explore a new pathway for clinical therapy of UC and to investigate the effect and therapeutic mechanism of ulinastatin in UC, we measured the changes of TNF-alpha, P-selectin, MDA ,SOD and colon mucosal ulceration index, also obseverd the expression of P-selectin and morphological changes before and after the treatment with ulinastatin for two weeks.Methods and Resultsl.The dynamic changes of TNF-alpha, P-selectin , MDA, SOD and colon mucosal ulceration indexA rat UC model was induced by Trinitrophenylmethylnitramine(TNBS), then we measured the dynamic changes of TNF-alpha, P-selectin, MDA ,SOD and colon mucosal ulceration index. We found that most rats showed symptoms of anorexia, decreasing of activity, diarrhea and hematochezia after 3 days induced by TNBS. These symptoms were alleviated after 7 days and disappeared after 21 days induced by TNBS. Compared with the control group, the serum levels of TNF-alpha and P-selectin were not changed on the 3rd day and the 21th day after induced by TNBS, but were significantly increased on the 7th day (TNF- a 2037.30+190.36 vs 933.13 + 188.24, P-selectin 0.429±0.142 vs 0.101 ±0.079 P<0.01). MDA activity in colon mucosa and colon mucosal ulceration index were significantly increased on the 3rd day after induced by TNBS (MDA 9.54± 1.45 vs 5.26 ± 1.98,index 3.40±0.70 vs 0.50±0.71,P<0.01 ), then decreased gradually. But SOD activity in colon mucosa were significantly decreased on the 3rd day (110.85±20.03 vs 211.26±23.45,P<0.01), then increased gradually. All were normal on the 21th day. The colon mucosal ulceration index was significant positively correlated with TNF-alpha, P-selectin and MDA, b...
Keywords/Search Tags:ulcerative colitis, tumor necrosis factor-alpha, P-selectin, malondialdehyde, superoxide dismutase, ulinastatin
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