Clinical Study On Treatment Of Steroid-dependent Ulcerative Colitis With Chinese Medicine And Mechanism Of Action Of Paeoniflorin Intervention

Objective To evaluate the clinical efficacy and safety of Chinese medicine for the treatment of steroid-dependent ulcerative colitis.Paeoniflorin and its induced Tol-DC intervention on naive T cells and UC models were conducted to explore the immune mechanism of Paeoniflorin.Method The clinical part:A multi-center,controlled method was used to treat patients with steroid-dependent ulcerative colitis.Azathioprine and Chinese medicine were given on the basis of 5-aminosalicylic acid and steroid therapy.The symptoms,mucosal lesions and clinical remission before and after treatment were observed,and evaluation of drug safety.Experimental part:To investigate the effect of paeoniflorin on the expression of surface molecular markers(MHC II,CD86)and cytokine IL-12 in mature dendritic cells.To observe the effects of paeoniflorin and its induced DCs on mouse naive T cells and TNBS-induced colitis.Flow cytometry was used to detect Treg/Th17 expression.ELISA,qPCR and Western blot were used to detect Foxp3,IL-10 and IL-17,IL-2 expression,pathological staining observed colon lesions.Results Clinical part:In the experimental group,steroid-free remission rate was 40.0%,and overall clinical efficiency was 85%.The control medicine group had steroid-free remission rate of 36.7%,and overall clinical effective rate was 76.7%.Both groups were relieved in terms of symptoms of diarrhea,abdominal pain,and pus and blood stool.There was no significant difference in the clinical efficacy,colonoscope appearance,mucosal healing rate,and improvement of erythrocyte sedimentation rate between the experimental group and the control group.However,adverse reaction events were lower in the experimental group than in the control group.Experimental part:Paeoniflorin can inhibit the upregulation of MHC II and CD86 in vitro and in vivo,and reduce the secretion of IL-12.The induced Tol-DC has the morphology and function of immature DC.DCs directly exposed to paeoniflorin reduced the ability of Th 17 to proliferate,IL-17 mRNA decreased,and also induced differentiation of naive CD4+ T cells to CD4+CD25+Foxp3+Treg and increased IL-10mRNA production.Paeoniflorin and paeoniflorin-induced Tol-DC reduced the expression of IL-17 and IL-2 genes and protein in TNBS-model mice,increased IL-10 and Foxp3 levels,and decreased Thl7 ratio.Conclusion Clinical trials show that Jianpibushen-qingchanglianyang recipe can be used for the treatment of patients with steroid-dependent ulcerative colitis.The efficacy is non-inferior to azathioprine,and the adverse reactions are low.Chinese medicine can be used as one of the alternative treatments for patients with refractory ulcerative colitis.Experimental studies have confirmed that paeoniflorin can induce the differentiation of naive T cells into Tregs by inducing the production of Tol-DC,up-regulate the secretion of anti-inflammatory cytokines IL-10,down-regulate the secretion of IL-17,reduce the intestinal inflammatory response,and restore Treg/Th17 balance,and make T cells clonal anergy.The establishment of immune tolerance is its mechanism of action in the treatment of ulcerative colitis.