Effects Of Curcumin On The Expression Of Toll Like Receptor4and NF-κB Signaling Pathway In Rats With Ulcerative Colitis

Objective:This experiment by studying the effect of curcumin on the expression levels oftoll-like receptor4,myeloid differentiation factor,Nuclear factor-κB in colon tissue ofUC rat models and interleukin-1and interleukin4in sera of UC rat models to discussthe the possible mechanism of curcumin,and to provide a theortical basis to clinic.Method:(1)rouping:Eighty clean grade of adult Sprague-Dawley (SD) rats,male and female inhalf and then randomly divided into seven groups(n=10): GroupA: the modelgroup.After the success of modeling,to different does of curcumin and5-aminosalicylic acid, GrpupB:Cur50mg/(kg d),GroupC:Cur100mg/(kg d), GrpupD: Cur200mg/(kg d),GrpupE:5-ASA100mg/(kg d),GrpupF:Cur100mg/(kg d) combined with5-ASA100mg/(kg d),GroupG:the control group.(2)Molding: SD rats model were manufactured by a compound method: trinitrobenzenesulfonic acid (TNBS)+ethanol method: After24hours, the rats wereanesthetized.With the silicone tube inserted in the anal about8cm,then irrigatedintestinal with injecting0.5ml TNBS (100mg/kg) and ethanol solution.(3)Dealing:Treatment group is respectively given different does of curcumin and5-amino salicylic acid.After continuous administration for14d,we gradedmacroscopical changes and colonic mucosal histological changes.The expression ofTLR4,Myd88and NF-κB in colonic mucosa were detected by using RT-PCR andwestern-blot,and the expression of IL-1and IL-4levels in sera were detected byELISA.Results:(1)General shape and pathology test results: the model group within8cm from the analhad colonic mucosa congestion, edema, erosion, necrosis,bowel wallthickening,ulceration. Form the result of HE staining,we could see that a largenumber of neutrophils, plasma cells and other inflammatory cell infiltrated,and ulceredge gland hyperplasia,glandular destruction,structural disorder and crypt abscessformation.(2)RT-PCR results: Compared with the control group,the UC group's TLR4 mRNA,Myd88mRNA,NF-κB mRNA in colonic mucosa were markedlyhigher(P<0.01). Compared with the UC group, TLR4mRNA,Myd88mRNA,NF-κB mRNA in group B to E decreased(P<0.01). Furthermore,there was nosignificant difference(P>0.05) between the group D and the group E, and theexpression of group F reduced the most.(3)Western blot: Compared with the control group,the UC group's TLR4,Myd88,NF-κBprotein levels in colonic mucosa were markedly higher. Compared with the UCgroup,the TLR4,Myd88,NF-κB protein levels in group B to E decreased, and theexpression of group F reduced the most.(4)ELISA results: Compared with the control group, the UC group IL-1levels in serawas markedly higher(P<0.01),IL-4was decreased(P<0.01). Compared with the UCgroup,IL-1levels in group B to E decreased,IL-4levels was higher(P<0.05).Furthermore,there was no significant difference between the group D and the groupE(P>0.05).Conclusion:(1) The expression level of TLR4, Myd88, and NF-κB in UC rat colonic mucosa cellsand inflammatory cells was significantly higher than the normal group,IL-1levelswas higher than normal group.All these suggest that TLR4, Myd88, NF-κB,IL-1andIL-4may be related with the occurrence and development of UC.(2) Curcumin is an effective therapy on TNBS-induced colitis in rats.Curcumin mayreduce colonic inflammation by decreasing the expression of TLR4,NF-κBsignaling pathway and improving the imblance of inflammatory factors. Thecurative effect of curcumin combined with5-ASA is superior to use5-ASA alone.