粪微生态制品移植治疗小鼠实验性结肠炎的研究

发布时间：2018-10-30 07:00

【摘要】：目的通过对小鼠实验性结肠炎模型实施粪微生态制品移植(fecal microbiota transplantation, FMT)治疗，探讨FMT对溃疡性结肠炎(ulcerative colitis, UC)的疗效及不同供体粪微生态制品对疗效有无影响。方法选用雄性BALB/c小鼠经葡聚糖硫酸钠(dextran sulfate sodium, DSS)诱导建立实验性结肠炎模型,将模型小鼠随机分为对照组、自体粪微生态制品移植组、异体单一供体粪微生态制品移植组和异体混合供体粪微生态制品移植组。自体粪微生态制品移植组、异体单一供体粪微生态制品移植组和异体混合供体粪微生态制品移植组分别经灌胃法移植自体建模前预留粪便混悬液、异体单一供体小鼠粪便混悬液和异体多只供体小鼠混合粪便混悬液，粪便混悬液均经-80℃冻存1-2周,对照组等量生理盐水灌胃。观察比较小鼠一般情况、体重变化、疾病活动指数(disease activity index, DAI)变化,取同一部位结肠观察比较结肠病理情况,对小鼠建模前、建模后和灌胃后的粪便标本16SrDNA的V3+V4区进行测序分析,研究其菌群结构变化。结果自体粪微生态制品移植组、异体单一供体粪微生态制品移植组和异体混合供体粪微生态制品移植组小鼠溃疡性结肠炎病情均比对照组显著好转,小鼠体重增加、DAI降低及结肠病理评分降低均与对照组有显著差异;建模后及FMT治疗后小鼠肠道菌群结构均发生变化，自体粪微生态制品移植组经治疗后与建模前肠道菌群结构最接近。自体粪微生态制品移植组、异体单一供体粪微生态制品移植组和异体混合供体粪微生态制品移植组小鼠体重和疾病活动指数(DAI)无明显差别,但异体单一供体粪微生态制品移植组和异体混合供体粪微生态制品移植组小鼠结肠病理评分高于自体粪微生态制品移植组,病理切片观察可见异体供体粪微生态制品移植组小鼠结肠炎性细胞浸润比自体粪微生态移植组明显。结论FMT可通过调节肠道菌群结构治疗DSS诱导的小鼠实验性结肠炎;冻存1-2周的粪便仍然具有治疗作用;FMT的治疗效果与供体的肠道菌群结构有关,与患病前肠道菌群结构越接近的供体粪便制品可能有更好的治疗效果;多个异体供体的混合粪便与单一供体FMT治疗效果无明显差别。
[Abstract]:Objective to investigate the therapeutic effect of FMT on ulcerative colitis (ulcerative colitis, UC) and the effect of different donor faecal microecological products on the effect of transplants of fecal microecological products (fecal microbiota transplantation, FMT) on experimental colitis in mice. Methods the experimental colitis model was established in male BALB/c mice induced by dextran sulfate (dextran sulfate sodium, DSS). The model mice were randomly divided into control group and autogenous faecal microecological product transplantation group. Allogeneic single donor faecal microecological product transplantation group and allogeneic mixed donor fecal microecological product transplantation group. The fecal suspension was reserved before autotransplantation of autogenous faecal microecological products, allogeneic single donor faecal microecological products transplantation group and allogeneic mixed donor faecal microecological products transplantation group, respectively. The fecal suspension of allogeneic single donor mice and allogeneic mice mixed with fecal suspension were frozen at -80 鈩，

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