The Research On The Relationship Between PAR-2and Cox-2Expressions In The Intestinal Mucosa Of Patients With Ulcerative Colitis

Research objectives:The etiology and pathogenesis of Ulcerative colitis (UC) is relatively complicated. Colorectal cancer is a common malignant tumor in digestive tract; in recent years the incidence of colorectal cancer shows a rising trend, however its pathogenesis is not fully clear. Colorectal cancer can be caused by many factors, such as heredity, inflammation, diet, genetic abnormality. Etc. Among which the repeating stimulate proliferation from chronic inflammation lesions on colorectal mucosa is an important one. UC is generally recognized as a very high risk factor for causing colorectal cancer, which can be finally developed into cancer by the chronic inflammation-atypical hyperplasia-cancer mode, the inflammatory factor plays an important role in this procession. The further study of the pathogenesis of UC is expected to intervene in the occurrence and development of UC, then achieve the purpose of prevention and treatment of ulcerative colitis associated colorectal cancer (UCACC). Therefor in order to controlling and reducing the incidence of colorectal cancer, prevention and treatment of ulcerative colitis is a important way.Protease activated receptors(PAR-S) is a kind of G-protein-coupled receptor, the activating of PAR-2can produce a variety of biological effects, including inflammation, vasodilation, specific regulating vascular proliferation, as well as proliferation, infiltration and migration of colorectal cancer cell. In animal experiments, the activating of the PAR-2in UC tissue will cause the release of TNF, Interleukin IL-1etc, and they all participate in the occurrence and development of UC and its canceration. Cyclooxygenas(COX) is a rate-limiting enzyme which can catalyse Arachidonic acid metabolizing into prostaglandin(PG) and other eicosanoids. COX-2can be inducted by many inflammatory mediators and cytokines, and its expression is increased in inflammation parts and tumor tissue,it plays an important role in inflammation cell proliferation and differentiation,it could also participate in the development of UC and colon cancer. Experimentation proves that COX-2and its metabolite PGE2plays an important role in the development of colorectal cancer; Lots of studies have demonstrated that COX-2inhibitors such as Nonsteroid anti-inflammatory drugs(NSAIDs) could inhibit the growth of tumor by many ways, thereby reducing the incidence of colorectal cancerPAR-2and COX-2are both involved in the development of UC and colorectal cancer. Study of the expression of these two factors together in human intestinal mucosa of UC was not reported at home and abroad. Our purpose is to detect and analyse the significance and relevance of the expreesions of PAR-2and COX-2in human colon mucosa tissue of UC, and then investigate new ways to prevent and treat UC and colorectal cancer.Research method:Experiment groups consisted of:UC group (36cases) and control group(33cases).Firstly we figure out the clinical severity and the extent of disease of UC patients, and take biopsy from the two groups by endoscope(lesion tissue of UC patients, normal intestinal mucosa of control group), then make conventional histopathological examination(UC pathologic stage) and Immunohistochemistry inspection, and analyse the expression and relevance of PAR-2and COX-2in the tissue. Finally Normal treatment for UC patients(use mesalazine or combining glucocorticoids local enema or systemic administration for8weeks), then to recheck coloscopy and examine biopsy again.Results:1. The difference of age and gender, between the33check-up healthy cases of control group and the UC group is not statistically significant(P>0.05), which are comparable.2. The expression of PAR-2and COX-2in severe UC group is higer than moderate UC group, mild UC group and control group (P<0.05); The expression of PAR-2and COX-2in lesion tissue is higher than in normal-appearing tissue obviously (P<0.01). After normal treatment, the expression of PAR-2and COX-2is decreasing obviously (P<0.01)3. The expression of PAR-2in UC pathological grade Ⅰ～Ⅳ group is higer than the control group (P<0.05), expression of PAR-2in grade Ⅲ～Ⅳ group is higher than grade Ⅰ～Ⅱ group (P<0.05); the expression of COX-2in pathological grade Ⅲ-IV group is obviously higher than grade Ⅰ～Ⅱ group and control group (P<0.05, P<0.01), expression of COX-2in grade Ⅰ～Ⅱ group is higher than the control group, but there is no significant differences (P>0.05).4. The expression of PAR-2in colon mucosa tissue has a positive relevent with COX-2(r=0.501, P<0.01); and they both are positive relevent with UC pathology stage.(r=0.366of PAR-2and r=0.378of COX-2; P<0.05both)Conclusion:1. The expression of PAR-2and COX-2in UC group is higher than those in the control group, they both are increasing gradually by the increasing of UC lesion degree, and have a positive relevent with UC pathology stage; expression of PAR-2and COX-2in lesion tissue is obviously higher than that in normal-appearing tissue; After normal treatment, the expression of PAR-2and COX-2is decreasing obviously.2. COX-2plays a complicated role in the pathogenesis of UC, it may work in the early stage or in the stage with minimal inflammation, and the correlation with disease course is not conspicuous, with the development of the patient’s condition, various of inflammatory medium and cytokine is released, it make the COX-2expresses excessively, and then show the correlation with disease course. Its mechanism of action needs to be further discussed.3. Expression of PAR-2and COX-2in UC colon mucosa tissue are positively correlated, considering that they are related by inflammatory medium and cytokine, and then to promote the development of UC together. On that basis, PAR-2, inflammatory factors, TF and PGE2jointly promote the develpment of UC associated colorectal cancer. 4. PAR-2and COX-2are expected to be target sites in interference the occurrence and the development of UC, cooperating with detection and treatment. To achieve the purpose of preventing and curing UCACC.