布拉氏酵母菌干预急性肝衰竭小鼠肠道菌群机制研究

发布时间：2018-06-24 03:29

本文选题：肠道菌群 + 布拉氏酵母菌　；参考：《贵州医科大学》2017年博士论文

【摘要】：目的:拟利用分子生物学方法深入探索肝衰竭时肠道菌群的变化,并采用布拉氏酵母菌干预肝衰竭时肠道菌群的变化,探讨其缓解肝衰竭的可行性。方法:选雄性健康BALB/C小鼠,试验设计如下:1)正常对照组(K组);2)急性肝衰竭组(M组);3)布拉氏酵母菌对照组(G组);4)布拉氏酵母菌预防组(H);5)布拉氏酵母菌治疗组(I组)。注射D-氨基半乳糖复制急性肝衰竭模型,注射36hr后处死小鼠,取血液和肝脏样品。采集小鼠血检测ALT,AST,TBiL,PTA,解剖切取小鼠肝脏做HE染色,取小鼠口腔、胃、结肠、回肠盥洗液,粪便,使用illumina高通量测序仪测定16S rDNA做细菌多样性分析,采集肝组织做RNA-seq转录组测序。结果:1、肝衰竭小鼠与健康对照小鼠消化道菌群存在明显差异,以回肠差异最为明显,肝衰竭小鼠肠道菌群多样性明显降低,在门水平拟杆菌增多、厚壁菌门、变形菌门减少。2、布拉氏酵母菌能增加肠道菌群多样性,促进丙酸杆菌、毛螺菌科等的生长,能抑制S24-7、理研科菌等生长。3、表达谱功能富集分析表明,布拉氏酵母菌引起表达基因变化主要涉及细胞凋亡、炎症反应、自身免疫及与胆固醇运输相关信号通路。富集的信号通路中TGF-beta信号通路鲜见与肝衰的相关性报道,通过对其介导的分子信号分析发现,布拉氏酵母菌可下调TGF-beta/Smad基因表达和蛋白质生成。结论:急性肝衰竭时肠道菌落发生显著改变,尤其在回肠部,布拉氏酵母菌可通过调节肠道菌群和抑制TGF-beta、Smad2、3、8的mRNA及蛋白质表达,从而缓解D氨基半乳糖所致的肝衰。
[Abstract]:Objective: To explore the changes of intestinal microflora in liver failure with molecular biological methods, and to explore the feasibility of the changes of intestinal microflora in the treatment of liver failure by yeast bacteria. Methods: male healthy BALB/C mice were selected as following: 1) normal control group (group K); 2) acute liver failure group (group M); 3) The yeast control group (group G), 4) the yeast Bacillus prevention group (H); 5) the yeast group (group I). The mice were injected with D- amino galactose to copy the acute liver failure model. After the injection of 36hr, the mice were killed and the blood and liver samples were taken. The mice blood was collected to detect ALT, AST, TBiL, PTA, and the mice liver was dissected for HE staining, and the oral, stomach, knot of mice's mouth, stomach, knot were taken. Intestinal, ileum lotion, feces, using Illumina high throughput sequencing instrument to determine 16S rDNA to do bacterial diversity analysis, and collect liver tissue to do RNA-seq transcriptional group sequencing. Results: 1, liver failure mice and healthy control mice have obvious differences in digestive tract bacteria group, the most obvious in the ileum, liver failure mice intestinal microflora diversity obviously decreased, The level of bacteriobacteria was increased, the phylum thickens and the deformable bacteria were reduced by.2, and the yeast could increase the diversity of the intestinal flora, promote the growth of propionus, and the growth of the family of the family hairy stud and so on. It could inhibit the growth of S24-7, the growth of.3, and the enrichment analysis of the expression spectrum showed that the expression gene changes mainly involved cell apoptosis and inflammation. Reaction, autoimmunity and signaling pathways associated with cholesterol transport. The correlation between TGF-beta signaling pathway and liver failure in the enriched signaling pathway is rarely reported. By its mediated molecular signal analysis, it is found that yeast can down regulate the expression of TGF-beta/Smad gene and protein production. Conclusion: intestinal colonies occur in acute liver failure. In the ileum, especially in the ileum, brachyeasts can alleviate the liver failure caused by D amino galactose by regulating the intestinal flora and inhibiting the expression of mRNA and protein of TGF-beta, Smad2,3,8.
【学位授予单位】：贵州医科大学
【学位级别】：博士
【学位授予年份】：2017
【分类号】：R575.3

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