| In recent years some researches have shown that p-glycoprotein (P-gp), the expression product of multi-drug resistance (MDR) genes relates to the incidence of ulcerative colitis. Differentiation level of multipotent progenitor stem cells of the immune system also affects the expression of P-gp. The most primitive hematopoietic stem cells have the highest p-gp expression. In the human body, P-gp is a kind of important transport protein with significant physiological functions, including detoxifying normal tissue, removing toxic substances, secreting hormone, transporting material and resisting exogenous toxin damage, etc. There are significant individual differences in the P-gp expression and differences also exist in the expression of p-gp in the same tissue.The study is aimed to discuss the relationship between MDR genes and the disease behavior of ulcerative colitis; the drugs influence on the expression of MDR genes; the relationship between the expression of MDR genes and the immune state of ulcerative colitis, and thus provide the theoretical and practical basis for diagnosis, treatment, and prevention of ulcerative colitis. Part 1 The Study on the Relationship between the expression of multidrug-resistant genes and disease behavior in ulcerative colitisObjective:To study the expression of P-gp, the product of MDR genes in the tissue of ulcerative colitis and the relationship between disease behavior in ulcerative colitis.Methods:Immunohistochemical techniques were applied to study the relationship between P-gp, the MDR expression product of ulcerative colitis and disease course, clinical stage, disease severity, clinical type, lesion extent, extraintestinal manifestations, and the other disease behaviors of ulcerative colitis.Results:1. Positive expression rate of p-gp in the patients with ulcerative colitis was significantly lower than that in the normal control group (P<0.05). Positive expression rates of p-gp were significantly lower after treatment of 12,18 and 24 months than that before treatment (P<0.05).2. Positive expression rates of p-gp at remission and active stage were significantly lower than that in the normal control group (P<0.05). There was no statistical significance in the difference between the expression rates at the remission and the active stage of ulcerative colitis (P<0.05). There was no statistical significance in the difference between the expression rates of the mild ulcerative colitis and the moderate and severe ulcerative colitis at active stage (P>0.05).3. Positive expression rate of P-gp in the acute fulminant ulcerative colitis as significantly lower than that in the recent-onset patients (P<0.05). There was no statistical significance in the difference in expression rates of the chronic persistent and chronic persistent and the recent-onset type (P>0.05).4. There was no statistical significance in the difference between positive expression rates of P-gp in sigmoideum, left colon, extensive colon, entire colon lesion and in rectum lesion (P>0.05). There was no statistical significance in the difference between positive expression rates of P-gp in ulcerative colitis without extraintestinal manifestations and with extraintestinal manifestations (P>0.05).Conclusion:1. Positive expression rate of P-gp dropped gradually with the extended course of ulcerative colitis, especially after treatment of 12,18 and 24 months.2. Positive expression rate of P-gp in ulcerative colitis was irrelevant to the active stage and severity degree.3. Positive expression rates of P-gp of all clinical types were significantly than that in the normal control group, especially the acute fulminant type. Positive expression rate of P-gp was irrelevant to extraintestinal manifestations and lesion extent of ulcerative colitis.Part 2 The study on the drugs influence on the expression of multidrug-resistant genes in ulcerative colitisObjective:To study the influence of amino salicylic acid, glucocorticoid and immunosuppressant therapeutic drugs on the expression of multidrug-resistant genes in ulcerative colitis.Methods:Immunohistochemical and reverse transcription-polymerase chain reaction (RT-PCR) methods were applied to study the influence of amino salicylic acid, glucocorticoide and immunosuppressant therapeutic drugs on expression of the multidrug-resistant-1(MDR1) and its expression product P-gp.Results:1. There was no statistical significance in the difference between positive expression rates of MDR1 genes and P-gp before and after amino salicylic acid treatment (P>0.05).2. There was no statistical significance in the difference of the expression quantity or rates between the group before ineffective glucocorticoide and immunosuppressant drugs treatment and the normal control group (P>0.05). Compared with the normal control group, the expression quantity or rate of the group after ineffective treatment was significantly higher (P<0.05).The difference of the expression quantity or rate of the group after ineffective treatment was statistically significant, compared with the normal control group (P<0.05). There was statistical significance in the difference of expression quantity and rate in the group before and after ineffective treatment and the group before and after effective treatment (P<0.05).Conclusion:Immunohistochemical and reverse transcription-polymerase chain reaction (RT-PCR) research methods indicated amino salicylic acid therapeutic drugs did not affect expression of the multidrug-resistant-1 (MDR1) and P-gp in ulcerative colitis. Multidrug-resistant-1 (MDR1) and P-gp in ulcerative colitis were significantly higher in the group after the ineffective glucocorticoide and immunosuppressant treatment.Part 3 The relationship between the expression of multidrug-resistant genes and immune state in ulcerative colitis.Objective:To study the relationship between the expression of multidrug-resistant genes and immune state in human's ulcerative colitis.Methods:The research methods including, double antibody sandwich ABC-ELISA method for measuring serum IL-8 levels, ABC-ELISA ways assaying blood serum IL-8 content, colorimetric methods for detecting colon mucosa NO content and NOS activity, flow cytometry for detecting peripheral blood CD4+ CD25+T cell subset percentage were applied to discuss the relationship between the expression of multidrug-resistant genes and immune state in human's ulcerative colitis.Results:Compared with P-gp negative patients P-gp positive patients'NO content and NOS activity were significantly higher in moderate and severe patients at active stage and in the recent-onset, chronic relapsed, chronic persistent, and acute fulminant types (P<0.05). Peripheral blood CD4+-,CD25+T cell subset percentage were significantly lower in the severe patients of active stage and acute fulminant type (P<0.05).Conclusion:Colon mucosa NO content, NOS activity and blood serum IL-8 content were significantly higher in patients with ulcerative colitis except at remission stage. And compared with P-gp negative patients, P-gp positive patients'colon mucosa NO content and NOS activity and blood serum IL-8 content were significantly higher except at remission stage and the mild and moderate type at active stage. Peripheral blood CD4+,CD25+T cell subset percentage in ulcerative colitis were significantly lower in patients with patients with ulcerative colitis except at remission stage. Compared with P-gp negative patients, positive patients' peripheral blood CD4+,CD25+ T cell subset percentage were much lower except at remission stage and the mild and moderate type at active stage.Conclusions of the project:1. P-gp expression the product of multidrug-resistance genes (MDR1) is closely related with the prolonged course of ulcerative colitis, and P-gp expression rate drops.2. The active period of P-gp expression drops sharply, but has nothing to do with severity degree.3. P-gp expression lowers in the clinically recent-onset, chronic relapsed, chronic persistent types, and most obviously in the acute fulminant type.4. P-gp expression is irrelevant to extraintestinal manifestations and lesion extent in ulcerative colitis.5. Immunohistochemical and reverse transcription-polymerase chain reaction (RT-PCR) research methods show amino salicylic acid-5 therapeutic drugs do not affect the expression of multidrug-resistant-1(MDR1) and glucocorticoide and immunosuppressive drugs increase the expression of multidrug-resistant genes of ulcerative colitis.6. Compared with P-gp negative patients P-gp positive patients' colon mucosa NO content NOS activity and blood serum IL-8 content rise significantly higher, and peripheral blood CD4+,CD25+ T cell subset percentage drop significantly.The drop of multidrug resistance genes (MDR1) and its expression product P-gp may be one of the causes of ulcerative colitis, and affects the disease behavior. The rise of the expression of multidrug resistance genes to the ineffective treatment of the patients resistant to corticosteroids and immunosuppressive drugs shows corticosteroids and immunosuppressive drugs may increase the expression of multidrug resistance genes of the ulcerative colitis. Injury factors of immune system play an important role in the pathogenesis of ulcerative colitis and more important role for the patients with multidrug-resistant genes and the P-gp positive.
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