| Ulcerative colitis(UC), also known as chronic non-specific ulcerative colitis. The clinical manifestations are abdominal pain, diarrhea, mucus blood and pus, weight loss and fever. The disease etiology is not clear,generally considered to be driven by the occurrence of multiple factors,mainly due to inadequate immune response to gut microbes that occur on genetically susceptible host. The pathogenesis of UC involves many aspects, generally believed that UC is caused by chronic inflammation of the colonic mucosa: â‘ epithelial barrier damaged; â‘¡Intestinal bacteria damage intestinal immune system balance of intestinal tolerance flora;â‘¢immune response disorders; â‘£ genetic factors. Therefor, establish an appropriate animal model of the disease is a key step in basic research.With the continuous development of Chinese medicine, Chinese medicine treatment of UC achieved a certain effect, and fewer adverse reactions. Rhubarb is a Polygonaceae plant, it`s roots and rhizomes of Rheum, tanguticum rhubarb medicinal rhubarb. Its cold, bitter, can dispel heat laxative, cooling blood detoxification, stasis pass through. Studies have shown that rhubarb protect the gastrointestinal mucosa and anti gastrointestinal mucosal injury, anthraquinones ingredients have antibacterial anti-inflammatory effect. Therefore, Rhubarb treating UC has a higher theoretical significance and practical value. This study aims to investigate rhubarb suppositories effect of 2,4,6-trinitrobenzene sulfonic acid(TNBS)-induced and oxazolone(OXZ)-induced mice UC.Sulfasalazine(SASP) has effect of antibacterial anti-inflammatory and immune suppression on the intestinal wall. Now it`s commonly used in clinical treatment of UC drug, so it used as a positive control drug in this experiments. Suppository not only have the effect of lubricating,astringent, anti-bacterial anti-inflammatory, but also can play a systemic effect through the rectum absorption, and avoids first-pass effect of the liver, so we chose semi-synthetic fatty acid glycerides(SSFAG) as a substrate suppository drug treatment for UC in mice. In this experiment,448 healthy Kunming mice(♂), with TNBS and OXZ were respectively induced mouse UC model.1 Rhubarb quality testing, and quality Control of rhubarb suppository and sulfasalazine suppositoryRhubarb were respectively detected on character identification, thin layer chromatography(TLC) and high performance liquid(HPLC).Through TNBS-induced, OXZ-induced, healthy mice body temperature measurement, we determined the proportional of 36 type SSFAG and 38 type. According the process: molten matrixâ†'injection moldingâ†'perfusionâ†'scrapeâ†'unmouldingâ†'stripping to prepared. We performed all types of suppositories weight difference and melt time testing According to Chinese Pharmacopoeia(ChP) second Appendix â… D suppository formulation General Clauses.The results showed character and content of rhubarb consistent with ChP(2010 edition). Rhubarb and SASP suppositories suppositories melt time and weight difference are reached Ch P(2010 edition). The dissolution rate of Rhubarb 800 mg·kg-1 suppository, rhubarb 400 mg·kg-1suppository and rhubarb 200 mg·kg-1 suppository increased in turn.2 Effect of rhubarb suppository on TNBS-induced mouse model of UC224 healthy Kunming mice(♂) were chosen,and randomly divided into seven groups(n = 32), â… model group, â…¡SASP suppository group,â…¢rhubarb 800mg·kg-1 suppository group, â…£rhubarb 400mg·kg-1suppository group, â…¤rhubarb 200mg·kg-1 suppository group, â…¥blank suppository group, â…¦solvent control group. â… ~â…¤TNBS induced mice UC modeling: enemas 0.6% TNBS solution 0.1mL; â…¦solvent control group: enemas 50% ethanol 0.1mL; â…¥ blank suppository groups: no treatment; 6 mice were sacrificed after enema administered once at d1, d2,d3, d5, d7 in each group. Each group of mice were giving appropriate suppository after enema modeling in every night. We detect weight,diarrhea, and fecal occult blood situation in every day. Detection of Disease Activity Index(DAI), Colon Macroscopic Damage Index(CMDI)and Histopathological Score(HPS), and detects mouse colon tissue Myeloperoxidase(MPO) activity, Interleukin-4(IL-4) content, Tumor Necrosis Factor-α(TNF-α) levels.Compared with the control group, model group of the DAI, CMDI,HPS score and MPO activity in d1, d2, d3, d5, d7 was significantly lower(P <0.01, P <0.01, P <0.01, P <0.01), TNF-α expression and IL-4 content also have significant difference(P <0.01, P <0.01); compared with the blank suppository group, medicated suppository group(B~E) at d1, d2, d3,d5, d7 significantly decreased(P <0.01, P <0.01, P <0.01, P <0.01);compared with the SASP suppository group, rhubarb 200mg·kg-1suppository can significantly improve UC mice DAI, CMDI, HPS score and MPO activity, the TNF-α expression was also significantly reduced accordingly, IL-4 content differences.3 Effect of rhubarb suppository on OXZ-induced mouse model of UC224 healthy Kunming mice(♂) were chosen,the grouping same as TNBS-induced UC group. â… ~â…¤: skin applicator 1% OXZ solution(100% ethanol solution) 0.1mL once a day for 2d(sensitization), enemas0.5% OXZ(50% ethanol solution) 0.1mL in d7; â…¦solvent control group:skin applicator 100% ethanol 0.1ml once a day for 2d, enemas 50%ethanol 0.1ml in d7; â…¥ blank suppository groups: no treatment; 6 mice were sacrificed after enema administered once at d1~d5 in each group.Each group of mice after the enema modeling for testing, the same with TNBS-induced UC group.Compared with the control group, model group of the DAI, CMDI,HPS score and MPO activity in d1, d2, d3, d4, d5 was significantly lower(P <0.01, P <0.01, P <0.01, P <0.01), TNF-α expression and IL-4 content also have significant difference(P <0.01, P <0.01); compared with the blank suppository group, medicated suppository group at d1, d2, d3, d5,d7 significantly decreased(P <0.01, P <0.01, P <0.01, P <0.01);compared with the SASP suppository group, rhubarb 200mg·kg-1suppository can significantly improve UC mice DAI, CMDI, HPS score and MPO activity, the IL-4 content was also significantly reduced accordingly, TNF-α expression differences.We made in suppositories physicochemical properties Stability In the experiments, and it meet the quality requirements of medicinal suppository.TNBS and OXZ could induce mouse model of UC, TNBS-induced mouse UC with Th1-type inflammation dominated, OXZ UC in mice induced Th2-type inflammatory response with the main, and so,UC is a result that Th1 and Th2 imbalance adjusted. Rhubarb suppositories has a therapeutic effect in these two drug-induced UC mice, and rhubarb 200mg·kg-1suppository is better, but not as SASP suppositories. |
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