The Effect Of Kuijieling On The IL-23/IL-17 Axis In Ulcerative Colitis Rats

ObjectiveUlcerative colitis is intestinal inflammatory diseases,which is mainly mediated by abnormal intestinal immune response.The IL-23/IL-17 axis plays an important role in the immune-mediated disease,such as ulcerative colitis,the pathogenesis of systemic lupus erythematosus,rheumatoid arthritis.IL-23/IL-17 axis is always balance in the normal body and keep the body's immune system environment in a state of stability.Some pathogenic factors make IL-23/IL-17 axis dysfunctional,causing Th17 cells Excessive proliferation and differentiation,so that Th17 cells secrete overmuch inflammatory cytokine IL-17,etc,eventually led to the related inflammation reaction.Previous studies have discussed from Treg and Th17 related differentiation factor and the imbalance of Th17/Treg.This research mainly discusses the kuijieling targets and mechanisms of UC,from the regulation of kuijieling on the IL-23/IL-17 inflammation axis and the factors IL-21,ROR?t,STAT3.MethodSPF male SD rats were randomly divided into six group,about a blank control group,model control group,high-does KJL,medium-does KJL,low-does KJL,SASP group.Trinitro-benzene-sulfonic acid(TNBS)was used to establish UC rat model.After the drug treatment with KJL in three various dosage and SASP on 10 days,the UC rats were sacrificed and scraped their plasma and colonic mucosa.enzyme linked immunosorbent assay(ELISA)was used to assay the expression of IL-23,IL-17,IL-21.Real-time PCR was used to assay the expression of IL-23mRNA.Western blot was used to assay the the protein expression of ROR?t and STAT3.Result1.The content of IL-17 in plasma of model group were higher than that of normal group(P<0.01),and the expression of IL-17 in three dosage KJL groups and positive drug salazosulfapyridine(SASP)group were both significantly lower than that in model group(P<0.01).2.The content of IL-23 in plasma of model group in UC model rats were higher than that of normal group(P<0.01),and the content of IL-23 in three dosage KJL groups and positive drug SASP group were both significantly lower than that in model group(P<0.01).3.The content of IL-21 in plasma of model group in UC model rats were higher than that of normal group(P<0.05),and the expression of IL-21 in high and middle dosage KJL groups and SASP group were both significantly lower than that in model group(P<0.05,P<0.01).4.The expression of IL-17 in colonic mucosa of UC model rats in model group was significantly higher than that in normal group(P<0.01),which expression in high,middle and low dosage groups of KJL and SASP group were obviously lower than that in model group(P<0.01).5.The expression of IL-23 in colonic mucosa of model group was significantly higher than that in normal group(P<0.05),which expression in high,middle and low dosage groups of KJL were obviously lower than that in model group(P<0.05,P<0.01).6.The expression of IL-23mRNA in colonic mucosa of model group in UC model rats was significantly higher than that in normal group(P<0.01),which expression in high and middle dosage groups of KJL and SASP group were obviously lower than that in model group(P<0.01).7.The protein relative expression of ROR'y t in colonic mucosa of model group in UC model rats was higher than that in normal group(P<0.05),which relative expression in high,middle and low dosage groups of KJL and SASP group were obviously lower than that in model group(P<0.05,P<O.01).The protein relative expression of STAT3 in colonic mucosa of model group was higher than that in normal group(P<0.01),which relative expression in three dosage groups of KJL and SASP group were obviously lower than that in model group(P<0.05,P<0.01).ConclusionBased on the analysis of results,the main mechanism of the UC is the dysfunctional of IL-23/IL-17 axis in UC rat models.The large expression of IL-23 through activating STAT3 signaling pathways,promotes the expression of Th17 related cytokines IL-17.The heighten IL-21 through activation of STAT3 signaling pathway,raising ROR ? t express,ROR y t inducing by encoding gene expression of IL-17,increases the production of IL-17,Promoting the T cells to Th17 differentiation in the end.This STAT3--Th17--IL-21 autocrine loops is the operating mode.The kui jieling(KJL)in the treatment of UC could be lowegr the expression of IL-23,inhibition of STAT3 signaling pathway,thereby inhibiting transition active Th17 cells reduces the the secretion of cytokines,such as IL-17.At the same time,The kuijieling could be lower the expression of IL-21,inhibit STAT3 signaling pathway,reduce ROR?t induction of IL-17 genes encoding,thus reducing the production of IL-17.This is the mechanism of keeping normal function of the IL-23/IL-17 axis and killing UC.