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@#To investigate the pharmacodynamic effects and mechanism of Zhuling Jianpi capsule(Zhuling) on 2,4, 6-trinitrobenzene sulfonic acid (TNBS)-induced experimental colitis in rats.The experimental colitis model was established by enema with 2.5% TNBS.The rats were randomly divided into normal group,model group,Changyanning (180 mg/kg) group and Zhuling low-dose (40 mg/kg) group and Zhuling high-dose (120 mg/kg) group.After modeling,the rats were executed after 7 days of drug treatment.During this period,the disease activity status of the rats was observed,and the body weights of the rats were recorded daily.At the end of the experiment,the colonic tissues were obtained for the analysis of the expression of hematoxylin-eosin(HE) staining.The myeloperoxidase (MPO) enzyme activity,mRNA expression levels of inducible nitric oxide synthase (iNOS) and inflammatory cytokines (IL-6, IL-1β, IFN-γ, IL-10) were determined, and the levels of intestinal tight junction proteins and serum inflammatory factor levels were measured.The results showed that compared with model group, the administration of Zhuling significantly alleviated the weight loss and elevated the disease activity index (DAI) caused by TNBS, relieved the shortening, edema and pathological damage of colonic tissue, reduced inflammatory cell infiltration, destruction of crypt and loss of goblet cells, decreased the MPO enzyme activity of colonic tissue, iNOS and pro-inflammatory cytokines in colon, increased the levels of colonic tight junction protein (occludin, ZO-1), and decreased serum levels of inflammatory factors (IL-6,IL-1β).The results suggest that Zhuling administration ameliorates TNBS-induced experimental colitis in rats by decreasing the level of inflammatory factors and increasing the expression of intestinal tight junction proteins.This experiment could provide a theoretical basis for the clinical application of Zhuling.
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AIM: To investigate the effects of manganese superoxide dismutase mimic (MnSODm) on 2, 4, 6-trinitrobenzene sulfonic acid (TNBS) induced ulcerative colitis (UC) in rats and to probe into its underlying mechanism. METHODS: Wistar rats were randomly divided into blank group, model group, sulfasalazine (SASP, 500 mg/kg) group, and different doses of MnSODm (10, 20 and 40 mg/kg) groups. Ulcerative colitis was induced in rats by rectal administration of 100 mg/kg TNBS dissolved in 50% ethanol. Rats were killed after SASP and different doses of MnSODm treatment 7 days. The disease activity index (DAI) was recorded, and then the colonic injury and inflammation were assessed by the colon weight/length ratio and microscopic damage scores. The serum and colon tissues activities myeloperoxidase (MPO) were detected by biochemistry method. The activities of glutathione peroxidase (GSH-Px), inducible nitric oxide synthase (iNOS), and the levels of glutathione (GSH) and NO in colon tissues were also detected. The levels of TNF-α, IL-4 and IL-10 in the colon tissues were measure by ELISA. Western blot was undertaken to determine the phosphorylation levels of AKT and PI3K. RESULTS: Compared with the model group, the colonic weight/length ratios, microscopic damage scores and colon tissues and serum MPO activity were significantly decreased in MnSODm groups (P<0.05 or P<0.01). INOS, NO, TNF-α, PI3K, p-AKT levels in colon tissues were also significantly decreased in MnSODm treatment groups; while the activity of GSH-Px and the concentration of GSH, IL-4 and IL-10 obviously increased (P<0.05, P<0.01). CONCLUSION: MnSODm is protective against colitis via antioxidant activity and by inhibiting inflammatory mediators and then down-regulating PI3K/AKT signaling pathways.
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Objective: To investigate effect of Shaoyaotang on intestinal mucosal immune barrier induced by 2,4,6-trinitrobenzene sulphonic acid (TNBS) in rats with ulcerative colitis.Method: Sixty SD rats were randomly divided into normal group,model group,mesalazine group (0.067 mg·kg-1),low,medium and high-dose Shaoyaotang groups (1.8,3.6,7.2 g·kg-1).In the TNBS-induced ulcerative colitis model,saline,mesalazine,peony soup were administered by gavage for 7 days.Hematoxylin-eosin (HE) staining was used to detect the histopathological changes of colon tissue.The number of CD4+T lymphocytes and the expression of secretory immunoglobulin A (SIgA) in intestinal mucosa were detected by immunohistochemistry and Western blot.Result: Compared with normal group,the scores of intestinal mucosal injury and the pathological scores in model group increased significantly (P+T lymphocytes and SIgA in the intestinal mucosa of model group decreased significantly (PP+T lymphocytes and SIgA in the intestinal mucosa of rats in each group elevated significantly (PPP+T lymphocytes and SIgA protein in the intestinal mucosa of rats in middle and high doses Shaoyaotang groups increased significantly (PConclusion: Shaoyaotang can reduce the intestinal mucosal damage and protect the intestinal mucosal immune barrier by increasing the number of CD4+T cells and the expression of SIgA secretion in the intestinal mucosa.
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Objective To investigate the effect of Astragalus polysaccharides (APS) on 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis in rats and on dendritic cells (DCs) in mesenteric lymph nodes.Methods Forty-four male Sprague-Dawley rats were randomly divided into four groups (n = 11) using simple random sampling: normal control group, TNBS group, APS group, and 5-aminosalicylic acid (5-ASA) group.Experimental colitis was induced in rats by TNBS enema in the last three groups.Rats in APS and 5-ASA groups were treated by gavage with APS (0.75 g ? kg-1 ? d-1) and 5-ASA (100 mg ? kg-1 ? d-1) on the 10 consecutive days following TNBS administration.The rats were then sacrificed and the colonic inflammatory scores of rats were measured, including the scores of disease activity index ( DAI) , macroscopic lesions, and histological damages,as well as the activity of myeloperoxidase (MPO).The expressions of major histocompatibility complex class Ⅱ(MHC Ⅱ ) and costimulatory molecule CD86 on DCs were determined by flow cytometry.Results Compared with the TNBS group, APS group had significantly decreased scores of DAI ( P = 0.007 ) , macroscopic lesions (P =0.017), and histological damages (P = 0.016).Moreover, its level of the activity of MPO dropped but without statistical significance (P =0.183).TNBS group had significantly higher expressions of MHC Ⅱand CD86 molecules on DCs than the normal control group (P = 0.005, P = 0.008), APS group (P = 0.023, P = 0.018), and 5-ASA group (P = 0.017, P=0.013).Conclusion APS may attenuate TNBS-induced colitis in rats and downregulate the activation of DCs in mesenteric lymph nodes.
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@#Objective To investigate the effects of Astragalus polysaccarides (APS) on 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis in rats. Methods Forty male Sprague-Dawley rats were randomly divided into five groups (n = 8 ): control group, TNBS group, low-dose APS group, high-dose APS group, and prednisone group. Experimental colitis was induced in rats by enema administration of TNBS. Rats in APS and sions and histological damages were determined, and the activity of myeloperoxidase (MPO) was measured in the excised colonic tissues. Cytokine levels including interleukin (IL)-4 and IL-10 were determined by enzyme-linked immunosorbent assay. Results Both macroscopic lesions and histological colonic damages induced by TNBS were reduced by low-dose APS treatment. These were accompanied by significantly attenuated colonic MPO activity (P = 0. 03) and the increase of IL-4 and IL-10 levels. The macroscopic lesions and MPO activities of high-dose APS group were higher than TNBS group, histological damage and level of IL-4 were lower, and level of IL-10 was higher, but all without statistical significance. Levels of IL-4 and IL-10 were lower than those of TNBS group, but there was no significant difference between prednisone group and TNBS group. Levels of IL-4 and IL-10 were significantly lower in prednisone group than in control group ( P = 0. 049, P = 0. 001 ). Conclusions Different doses of APS have different effects on TNBS-induced colitis. Lower dose of APS has the therapeutic potential inexperimental colitis, while higher dose of APS may aggravate the disease.
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Objective To develop a model of inflammatory bowel disease in rats induced by 2,4,6-trinitrobenzenesulfonic acid(TNBS).Methods Fifty Wistar rats were randomly divided into three groups:model,mock model and normal group.2% TNBS,50% ethanol and physiological saline were administered per-rectum to each of the three groups,respectively.Feces,psychosis and appetite were observed,body weight and food eaten were recorded daily.Rats were killed after 3,6 and 14 d,and the colons were isolated and histological findings were examined.Results On the first day,rats in the model group had loose and bloody stools,and the symptoms lasted for about 8 days.Body weight and food eaten were markedly decreased for 7-10 days.Obvious pathological changes in the colon were observed on third day and heavier on sixth day,characterized by mucosal necrosis and transmutable inflammation.In the mock model group,the rats had loose stools on first day,and recovered on second day.Light pathological changes were found on third day.In the normal group,no pathological changes were found in colon.Conclusion Rats treated with TNBS showed obvious characters of inflammatory bowel disease,which could be used as a model in study on etiopathogenesis and evaluation effects of medicines.