Abstract:Objective:To construct ulcerative colitis (UC) model included by 2,4,6- trinitrobenzene sulfonic acid (TNBS) and oxazolone (OXZ) in mice and to observe the therapeutic effect of rhubarb suppository on ulcerative colitis.Methods：448 KM mice (♂) were randomized into 2 groups (n = 224) to construct TNBS and OXZ model. Kunming Mice in GroupⅠ(TNBS model group) were randomly divided into 7 subgroups (n=32) including A (TNBS model group), B (sulfasalazine (SASP) suppository group), C (800 mg·kg-1 rhubarb suppository group), D (400 mg·kg-1 rhubarb suppository group), E (200 mg·kg-1 rhubarb suppository group), F (blank suppository group) and G (TNBS solvent control group) . GroupⅠ(A ~ E) were treated with 0.6% TNBS solution 0.1 mL enema; GroupⅠ(F) had no treatment; GroupⅠ(G) with 50% ethanol 0.1 mL enema; 6 mice of each group were sacrificed after giving enema on d 1, d 2, d 3, d 5, and d 7. Mice in GroupⅡ(OXZ model group♂) were randomly divided into 7 subgroups (n=32) including A (TNBS model group), B (sulfasalazine (SASP) suppository group), C (800 mg·kg-1 rhubarb suppository group), D (400 mg·kg-1 rhubarb suppository group), E (200 mg·kg-1 rhubarb suppository group), F (blank suppository group) and G (TNBS solvent control group) . GroupⅡ(A~E) were treated with skin sensitization 1% OXZ solution (0.1 mL 100% ethanol solution) once a day, lasting two days (sensitization) and on the 7th day they were treated with OXZ at 0.5% (50% ethanol solution) 0.1 mL enema; GroupⅡ(F) had no treatment; GroupⅡ(G) with skin sensitization 100% ethanol 0.1 mL, once a day, lasting two days, and on the 7th day with 0.1 mL of 50% ethanol enema; 6 mice of each group were sacrificed after giving enema on the 1st, 2nd, 3rd, 4th, 5th day. We observed the Disease Activity Index (DAI), Colon Macroscopic Damage Index (CMDI) and Histopathological Score (HPS) score of the mice in GroupⅠand GroupⅡ, and determined the levels of Myeloperoxidase (MPO), Interleukin -4 ( IL-4) and Tumor Necrosis Factor -α (TNF-α) in colon tissues of mice.Results：Compared with GroupⅠ(G), the activity of DAI, CMDI, HPS and MPO, IL-4 content and TNF-α expression content in GroupⅠ(A) changed significantly on d 1, d 2, d 3, d 5, and d 7. In GroupⅠ, compared with blank suppository group (F) , the DAI, CMDI, HPS, MPO activity, IL-4 content, and TNF-α expression content of the mice in groups (B~E) had differences on d 1, d 2, d 3, d 5, d 7. Compared with SASP suppository group (B) in GroupⅠ, there were differences in (C~E) groups with different rhubarb doses on d 1, d 2, d 3, d 5, and d 7, in which the rhubarb 200 mg·kg-1 suppository group (E) had little difference from other rhubarb suppository groups. Compared with groupⅡ(G), the activity of DAI, CMDI, HPS and MPO , IL-4 content and TNF-αexpression content of the mice in GroupⅡ(A) had significant difference on d 1~5. Compared with blank suppository group (F) in GroupⅡ, the activity of DAI, CMDI, HPS and MPO, IL-4 content, and TNF-α expression content in mice of suppository group (B~E) took changes on d 1~5, and had significant changes in groups (C~E) with rhubarb. In GroupⅡ, compared with SASP suppository group (B), groups (C~E) with different doses of rhubarb had differences, in which rhubarb 200 mg·kg-1 suppository group (E) had little difference.Conclusion：Both TNBS and OXZ could induce mice model of ulcerative colitis. Rhubarb with different doses performed therapeutic effects on UC mice, and rhubarb with 200 mg·kg-1 dose did better, but not as good as the effect of SASP .

Key words:ulcerative colitis,2,4,6-trinitrobenzene sulfonic acid,Oxazolone,,rhubarb,suppository