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目的:探讨携带肝细胞生长因子基因的减毒鼠伤寒沙门茵对TNBS诱发大鼠实验性结肠炎模型外周血T细胞亚群和免疫球蛋白的影响。方法:50只Wistar大鼠经TNBS灌肠诱发溃疡性结肠炎模型,并随机分为4组:Ty治疗组、Typl-HGF治疗组、Yypl-GFP观察组、模型对照组,除模型对照组20只外,其余每组10只;另设生理盐水灌肠的正常对照组10只。造模后第3天各组灌胃进行治疗,依次给予1×109cfu的Ty、Typl-HGF、Typl-GFP茵液,每只0.5ml,隔日1次,模型和正常对照组给予同体积的100g/LNaHCO3。3次和6次灌胃后1周,各组分别采集全血,用流式细胞仪检测各组CD4+T、CD8+T、IgM、IgG1、IgA水平;Typl-GFP组观察目的基因的组织表达。结果:灌胃3次和6次后模型对照组与正常对照组相比CD4+T细胞均无明显变化,但CD8+T细胞下降明显(P<0.01),CD4+/CD8+T比值明显升高(P<0.05);Typl-HGF组3次灌胃后CD4+T低于模型组(P<0.05),6次灌胃后CD4+T、CD4+/CD8+T比值均明显低于模型对照组和Ty组(P<0.01,P<0.01,P<0.05,P<0.05)。灌胃3次和6次后模型对照组与正常对照组相比IgM、IgG1、IgA均明显增加(P<0.05,P<0.05,P<0.05,P<0.01,P<0.01,P<0.01);灌胃3次和6次Ty组与同期模型对照组、Typl-HGF组相比IgM明显增加(P<0.01,P<0.01),而6次Typl-HGF组与模型对照组相比IgM、IgG,明显降低(P<0.05,P<0.05)。在荧光显微镜下可观察到Typl-GFP茵液灌胃后在结肠组织GFP强表达。结论:大鼠实验性结肠炎发病过程中,机体免疫功能处于亢进状态,Typl-HGF能够抑制T细胞增殖和B淋巴细胞抗体的产生,它可能代表了一种新的药物用于治疗结肠炎疾病。
Objective: To investigate the effects of attenuated Salmonella typhimurium carrying hepatocyte growth factor gene on T lymphocyte subsets and immunoglobulins in TNBS-induced experimental colitis in rats. Methods: Fifty Wistar rats were induced by TNBS enema and divided into four groups at random: Ty treatment group, Typl-HGF treatment group, Yypl-GFP observation group, model control group, 20 rats in model control group , The rest of each group of 10; another normal saline enema control group of 10. On the 3rd day after model establishment, each group was treated with gavage by intragastric administration, followed by 1 × 109 cfu of Ty, Typl-HGF, Typl-GFP inoculum, 0.5 ml each time, once every other day, and the same volume of 100 g /LNaHCO3.3 times and 6 times one week after gavage, the whole blood samples were collected from each group, and the levels of CD4 + T, CD8 + T, IgM, IgG1 and IgA in each group were detected by flow cytometry; Tissue expression of genes. Results: Compared with the normal control group, there was no significant change in the CD4 + T cells in the model control group after 3 and 6 times of gavage, but the level of CD8 + T cells decreased significantly (P <0.01) and the ratio of CD4 + / CD8 + T increased significantly (P <0.05). The levels of CD4 + T and CD4 + / CD8 + T were significantly lower in the Typl-HGF group than those in the untreated group (P <0.05) And Ty group (P <0.01, P <0.01, P <0.05, P <0.05). Compared with the normal control group, the levels of IgM, IgG1 and IgA in the model control group increased significantly (P <0.05, P <0.05, P <0.05, P <0.01, P <0.01, P <0.01) (P <0.01, P <0.01). Compared with the model control group, the levels of IgM, IgG significantly decreased (P <0.05, P <0.05). In the fluorescence microscope can be observed Typl-GFP Yin fluid gavage in the colon GFP strong expression. Conclusion: The immune function of rats is hyperactive during the pathogenesis of experimental colitis. Typl-HGF can inhibit T cell proliferation and B lymphocyte antibody production, which may represent a new drug for the treatment of colitis .