Study On The Mechanism Of Colonic Selenoproteins In The Pathogenesis Of Colitis In Selenium Deficient Mice

Ulcerative colitis(UC)is a common chronic inflammatory disease of the digestive system,but its etiology is not clear.Oxidative stress and its induced inflammatory cell infiltration and abnormal immune response are important pathological mechanisms of the disease.Selenium is an important essential trace element,and its biological function is often mediated by various selenoproteins,which can participate in the regulation of cellular oxidative stress,antioxidant defense,immunity and inflammation and other biological processes.Selenium deficiency often occurs in patients with colitis,which may involve selenoprotein and various signal pathways closely related to inflammation and oxidative stress,but its molecular mechanism is not clear.Based on the above background,this study used colitis mice under selenium deficiency as a model to explore the mechanism of selenoprotein and its related pathways in the occurrence and development of inflammatory bowel disease.In this experiment,32 6-week-old male C57BL/6J mice were randomly divided into four groups: drinking water selenium group(CON-S,n=8),DSS selenium deficiency group(DSS-S,n=8),drinking water selenium deficiency group(CON-D,n=8)and DSS selenium deficiency group(DSS-D,n=8).The experimental cycle was 7 weeks.The animals in CON-S and DSS-S groups were fed with sufficient selenium diet,while CON-D and DSS-D were fed with selenium deficiency diet.In the last week,the animals in the DSS-S and DSS-D groups were given 2.0% sodium glucan sulfate(DSS).The main results are as follows:1.In the CON-S group,the mental state was good,the body weight increased slightly,the colon was not shortened and the tissue structure was clear,while in the CON-D group,the body weight decreased slightly and the intestinal tissue structure was slightly disordered.The activity of mice in DSS group decreased significantly,their body weight decreased significantly,and the intestinal structure was seriously damaged.There was no significant difference in severity between DSS-D group and DSS-S group.Compared with the DSS-S group,the serum pro-inflammatory factors in the DSS-D group were significantly up-regulated,the anti-inflammatory factors were significantly down-regulated,and the expressions of intestinal barrier-related genes ZO-2 and JAM were also down-regulated accordingly.At the same time,the mRNA expression levels of macrophage-related indexes i NOS and Itgax in the DSS-D group were significantly up-regulated by 56.1% and 37.5%,indicating that dietary selenium deficiency increased the inflammatory response in colitis mice.2.The activity of GPx in serum and colon in CON-D group was significantly lower than that in CON-S group,which indicated that the model of selenium deficiency was established.Compared with DSS-S group,dietary selenium deficiency decreased serum GPx,Grx and SOD by 55.3%,50% and 28.9%,respectively,and colonic GPx activity decreased by 56.7%.At the same time,mRNA,a gene related to oxidative stress in the colon of DSS-D group,also showed redox imbalance,indicating that selenium deficiency aggravates oxidative stress in mice.3.By detecting the relative expression levels of 24 selenoproteins mRNA in mice,it was found that the expression levels of GPX2,GPX3,DIO2,DIO3,SELENOH,SELENOM,SELENOW and SELENOP in colitis mice changed significantly under the intervention of dietary selenium deficiency,and the change of antioxidant selenase GPX2 which was highly expressed in intestine was the most obvious.Compared with the DSS-S group,the expression of GPX2 in the DSS-D group was up-regulated by 203.1%,and the Western blotting results were also consistent with the trend of PCR results.In addition,the expression of DIO2 and DIO3,which are important for the regulation of thyroid hormone,significantly interfered with dietary selenium deficiency in colitis mice.Compared with DSS-S group,DIO2 and DIO3 gene expression in DSS-D group was significantly up-regulated by 91.2% and 607.2%,respectively.4.The related indexes of PGE2 pathway in the intestinal tract of mice were detected,and the contents of COX-2,NOX2,PGE2 and the expression level of mPGES-1 synthase all changed significantly.Compared with the DSS-S group,the expression of mPGES-1gene in the DSS-D group was significantly up-regulated by 288.9%,and the result of Western blotting was consistent with that of Western blotting.At the same time,the content of PGE2 in colon also changed significantly.The content of PGE2 in DSS-D group was significantly increased by 27.5%,and the protein expression levels of COX-2 and NOX2 were further detected,which were 91% and 436.8% higher than those in DSS-S group and DSS-D group,respectively.In summary,based on phenotypic indexes such as disease activity index and tissue damage score,selenium deficiency treatment for 6 weeks could not aggravate the incidence of colitis in mice.However,the results of inflammatory and oxidative stress related factors in blood and tissue showed that dietary selenium deficiency significantly increased the level of inflammatory response and oxidative stress in colitis mice.At the same time,colonic selenoprotein and its mediated COX-2/mPGES-1/PGE2 signal pathway also changed significantly in selenium deficient mice.Therefore,selenium deficiency is one of the important inducements to aggravate the pathogenesis of colitis.Selenoprotein and its mediated COX-2/mPGES-1/PGE2 pathway play an important role in this regulation process,but the specific molecular mechanism of selenoprotein mediated oxidative stress and inflammatory response needs to be further studied.