Effect Of Xiezhuojiedu Decoction On Inflammatory Cytokines IL-10,TNF-α And NF-κB On Ulcerative Colitis Model Rats

Objective: The main objective of this study is to explore the effect of Xiezhuojiedu Decoction on inflammatory cytokines IL-10,TNF-αand NF-kB on Ulcerative Colitis Model Rats ,and compare the therapeutic effects with sulfasalazine tablets(SASP) , elucidate the possible mechanism of this decoction on Ulcerative Colitis ,so as to provide theoretical and practical basis for the treatment of Ulcerative Colitis.Method : 2 , 4 , 6-trinitrobenzene- sulfonic acid ,TNBS/ethanol combinative method of establishing model used to Induce animal models in Rat Ulcerative Colitis in this study, 40 healthy and clean SD Rats were taken ,which were male, weighing 200--220g and were randomly divided into 5 groups with 8 rats in each group. one group was chosen to be the control group ,the other 4 groups were given 30% Ethanol Solution which contains 30mg TNBS, 0.5ml each rat to make Ulcerative Colitis animal models, and they are separately named modeling group,SASP group,Xiezhuojiedu Decoction high dose group,Xiezhuojiedu Decoction low dose group . Three days after modal making, all the rats were administered by intragastric administration for 14 days. The control group, modeling group rats were given normal saline by gavage and observed the effect . I studied and discussed the experiment from three aspects: Experiment 1, observed the effect of Xiezhuojiedu Decoction on general condition and pathological effect on Ulcerative Colitis Model Rats; Experiment 2, observed the effect of Xiezhuojiedu Decoction on serum interleukin-10 and tumor necrosis factor TNF-αcontent on Ulcerative Colitis Model Rats; Experiment 3, observed the effect of Xiezhuojiedu Decoction on nuclear factor-kb expression on Ulcerative Colitis Model Rats. The main object of this study is to elucidate the possible mechanism of Xiezhuojiedu Decoction on Ulcerative Colitis .Results:1 Experiment 1 showed : the rats general condition changed differently in modeling group and all the treatment groups compared with the control group. All those mental status,activity condition,hair glossiness,appetite,defecate character,ect were better in Xiezhuojiedu Decoction high dose group than the other groups, and weight rose more quickly, too .The rats'CMDI score in modeling group increased significantly, compared with normal control group,the results had significant differences (P <0.01); compared with blank control group, the other groups had no differences (P> 0. 05); The rats'CMDI score in all Xiezhuojiedu Decoction groups and SASP group significantly decreased ,compared with the modeling group, they all had a very significant difference (P <0. 01). The rats' CMDI score in Xiezhuojiedu Decoction low dose group and SASP group had no significant differences (P> 0. 05). The rats'CMDI score in Xiezhuojiedu Decoction high dose group and SASP group had significant differences (P<0.01).2 , 4 ,6-trinitrobenzene- sulfonic acid, TNBS/ethanol combinative method of establishing model is easy , it had good reproducibility and the topathologic changes are similar to humans. the modeling group rats mucous layer deleted , congestion and edema,inflammatory cell infiltration were found in inflammatory cell infiltration;in traditional chinese medicine treatment groups and SASP group, the mucous layer was complete, congestion and edema and inflammatory cell infiltration were not found.2 Experiment 2 showed : compared with the serum IL-10 content in blank control group (65. 06±3. 53), modeling group (49. 72±4. 04), Xiezhuojiedu Decoction low dose group (61. 33±2. 83) , Xiezhuojiedu Decoction high dose group (65. 09±3. 44), SASP group (61. 21±3. 91) all had differences (P <0. 05);compared with the serum IL-10 content in modoling group , Xiezhuojiedu Decoction high dose group , SASP group all had differences (P <0. 01); Compared with the serum IL-10 content in SASP group, Xiezhuojiedu Decoction low dose group had no difference (P>0.05);Xiezhuojiedu Decoction high dose group had significant differences (P<0.01).Compared with serum TNF-αlevels in blank contral group (0. 89±0. 219) ,modeling group (1. 875±0. 359), Xiezhuojiedu Decoction low dose group (1. 324±0. 131 ), SASP group (1. 293±0. 139)had significant differences (P <0. 01), Xiezhuojiedu Decoction high dose group(1.043±0.126)had no differences; Compared with serum TNF-αlevels in modeling group , Xiezhuojiedu Decoction low dose group,Xiezhuojiedu Decoction high dose group, SASP group all had significant differences (P <0. 01); Compared with serum TNF-αlevels in SASP group, Xiezhuojiedu Decoction low dose grouphad no difference(sP>0.05), Xiezhuojiedu Decoction high dose group had significant differences (P<0.01).3 Experiment 3 showed : Compared with the NF-κBp65 expression in blank control group (0. 267±0. 04) , the NF-κBp65 expression in modeling group (0. 385±0. 071) had significantly increased and had significant difference (P <0. 01), the NF-κBp65 expression in Xiezhuojiedu Decoction low dose group (0. 314±0. 034) and SASP group (0. 323±0. 031) had differences (P <0. 05), Xiezhuojiedu Decoction high dose group (0. 261±0. 025) had no differences (P> 0. 05). Compared with the expression of NF-κBp65 in modeling group , Xiezhuojiedu Decoction low dose group, Xiezhuojiedu Decoction high dose group SASP groups were significantly different (P <0. 01). Compared with the expression of NF-κBp65 in SASP group, Xiezhuojiedu Decoction low dose group had no significant differences (P> 0. 05), Xiezhuojiedu Decoction low dose group had significantly differences(P <0. 01). Conclusion : It is considered that the Pathogenesis of this disease is : turbidity toxin stasis , lipid membranes and superficial venules injury, blood and meat rot, block and suppurate;after a long time, turbidity toxin is cohesive, intestinal conduction loses control and then this disease occurres. Turbidity toxin is not only a kind of pathogenic factor,bu also a kind of pathological product ,and it has the double effects of starting and aggravating the disease. Turbidity toxin can easily damage healthy energy and go deeply into viscera,adheres and relays, disappears difficultly, so it becomes the key to the active stage of ulcerative colitis.Although in the remission stage of ulcerative colitis,it is the stalemate stage of turbidity toxin and healthy energy or deficiency formatting because of toxin,turbidity toxin hardly leaving. Ulcerative Colitis Models were successfully made during the experiment, we observed the effect of Chinese medicine Xiezhuojiedu Decoction on Ulcerative Colitis Model Rats and the intervention effect on inflammatory response ,and observed the change of pre and post treatment. The research results showed that: Xiezhuojiedu Decoction can improve the rats'nutritional status, promote intestinal digestion and absorption,increase the weight , improve IL-10expression level,decreaseTNF-αcontent,decrease NF-κBp65expression level , consequently inhibit inflammatory cells,repair the damaged intestinal mucosa, relieve the inflammation, accelerate the ulcer healing. The results proved the effect of Chinese medicine Xiezhuojiedu Decoction on Ulcerative Colitis Model Rats, the therapeutic mechanism is possibaly related to its influence on some inflammatory factors,so as to widen Notion for treating ulcerative colitis by traditional chinese medicine.