| ?Objective?Ulcerative colitis is a kind of inflammatory bowel disease with the symptom of inflammatory mucosal pus and bloody stool,accompanied by abdominal pain,diarrhea and other symptoms.Years of research found that the pathogenesis is closely related to the autoimmune system,and the abnormal function of Th17 cells plays an important role in the pathogenesis of ulcerative colitis.At present,many studies have also found that in the pathogenesis of ulcerative colitis,the differentiation and dysfunction of Th17 cells are closely related to a class of non-coding RNA,miRNAs.Among them,miR-155 plays an important role in influencing the differentiation and function of Th17 cells.However,the exact mechanism by which miR-155 affects Th17 cell differentiation and function in colonic mucosa of ulcerative colitis is not fully understood.The purpose of this experiment is to investigate the effects of miR-155 on the differentiation and function of Th17 cells during colonic colonization in TNBS-induced rat colitis model and the effect of Compound Sophorae Flavescentis Decoction in this process.This experiment not only explored the possible mechanism of ulcerative colitis,but also explored new ways for the treatment of ulcerative colitis.?Methods?Sixty SDF rats(6-8 weeks)were randomly divided into six groups: normal control group,model group,miR-155 inhibition group,negative virus control group,mesalazine group and compound Sophorae Flavescentis Decoction group.On the first day of the experiment,five groups of rats outside the normal group were given TNBS enema for modeling.In the third day,all the rats of miR-155 inhibition group and the negative virus control group were given corresponding virus enema.And starting from the third day,Mesalazine group rats were given daily mesalazine gavage,and Compound Sophorae Flavescentis group rats were given daily Chinese herbal compound Sophorae FlavescentisDecoction gavage.On the tenth day of the experiment,the rats in each group were sacrificed after anesthesia,and the levels of Th17 cells in the spleen and mesenteric lymph nodes were determined by flow cytometry.The colon tissues of the rats in each group were fixed and subjected to HE staining and immunohistochemistry to determine the content of Jarid2.The expression of miR-155 was detected by hybridization.The frozen sections were used to observe the virus uptake.The protein contents of IL-17 A,IL-17 F,TGF-?,IL-6 and IL-21 were detected by Elisa.IL-6,ROR-?t,notch1 and Jarid2 mRNA and miR-155 content were detected by RT-PCR;western blot measured Jarid2 and notch1 protein content.?Results?After TNBS modeling,we observed the DAI of rats in each group.Compared with the normal group,the DAI of rats in the first three days of the experiment increased obviously,which indicated that the modeling was successful.After the third day of intervention,compared with the model group,the DAI of mi R-155 inhibition group,compound Sophorae Flavescentis decoction group and mesalazine group decreased significantly.Compared with the normal group,the proportion of Th17 cells in the spleenand mesenteric lymph nodes of the model group was significantly increased(P <0,05),the differentiation of Th17 cells and the function-related cytokines IL-17 A,IL-17 F,IL-21 and IL-6(P <0.05),the content of TGF-? was significantly lower(P <0,05),the mRNA of IL-6 and ROR-?t and the expression of miR-155 were also significantly increased(P<0,05),TGF-? mRNA content was significantly lower(P <0,05).Compared with the model group,the expressions of the above-mentioned(except TGF-?)protein or mRNA of the miR-155 inhibition group,the mesalazine group and the compound Sophorae Flavescentis decoction group were significantly lower(P <0,05),while the TGF-? and its mRNA expression were significantly increased(P <0,05).Compared with normal group,the protein and mRNA expression of Jarid2 in the model group decreased significantly(P<0,05),while the expression of notch1 protein and mRNA increased significantly(P<0,05).Compared with the model group,the protein and mRNA expression of Jarid2 in the miR-155 inhibition group,Mesalazine group and Compound Sophorae Flavescentis decoction group were significantly increased(P <0,05),while the notch1 protein and mRNA expression was significantly Decreased(P <0,05).?Conclusions?1.miR-155 is involved in the development of colitis in rats with ulcerative colitis induced by TNBS;2.miR-155 inhibition can relieve TNBS induced ulcerative colon;3.miR-155 has effect on the differentiation and function of Th17 cells in colonic mucosa of TNBS-induced colitis in rats;4.miR-155 affects Th17 cell differentiation through Jarid2 / notch1 axis;5.Compound Sophorae Flavescentis decoction can affect mRNA-155 expression and relieve TNBS-induced ulcerative colitis... |
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