布拉氏酵母菌干預(yù)急性肝衰竭小鼠腸道菌群機(jī)制研究
本文選題:腸道菌群 + 布拉氏酵母菌。 參考:《貴州醫(yī)科大學(xué)》2017年博士論文
【摘要】:目的:擬利用分子生物學(xué)方法深入探索肝衰竭時(shí)腸道菌群的變化,并采用布拉氏酵母菌干預(yù)肝衰竭時(shí)腸道菌群的變化,探討其緩解肝衰竭的可行性。方法:選雄性健康BALB/C小鼠,試驗(yàn)設(shè)計(jì)如下:1)正常對(duì)照組(K組);2)急性肝衰竭組(M組);3)布拉氏酵母菌對(duì)照組(G組);4)布拉氏酵母菌預(yù)防組(H);5)布拉氏酵母菌治療組(I組)。注射D-氨基半乳糖復(fù)制急性肝衰竭模型,注射36hr后處死小鼠,取血液和肝臟樣品。采集小鼠血檢測(cè)ALT,AST,TBiL,PTA,解剖切取小鼠肝臟做HE染色,取小鼠口腔、胃、結(jié)腸、回腸盥洗液,糞便,使用illumina高通量測(cè)序儀測(cè)定16S rDNA做細(xì)菌多樣性分析,采集肝組織做RNA-seq轉(zhuǎn)錄組測(cè)序。結(jié)果:1、肝衰竭小鼠與健康對(duì)照小鼠消化道菌群存在明顯差異,以回腸差異最為明顯,肝衰竭小鼠腸道菌群多樣性明顯降低,在門水平擬桿菌增多、厚壁菌門、變形菌門減少。2、布拉氏酵母菌能增加腸道菌群多樣性,促進(jìn)丙酸桿菌、毛螺菌科等的生長(zhǎng),能抑制S24-7、理研科菌等生長(zhǎng)。3、表達(dá)譜功能富集分析表明,布拉氏酵母菌引起表達(dá)基因變化主要涉及細(xì)胞凋亡、炎癥反應(yīng)、自身免疫及與膽固醇運(yùn)輸相關(guān)信號(hào)通路。富集的信號(hào)通路中TGF-beta信號(hào)通路鮮見與肝衰的相關(guān)性報(bào)道,通過(guò)對(duì)其介導(dǎo)的分子信號(hào)分析發(fā)現(xiàn),布拉氏酵母菌可下調(diào)TGF-beta/Smad基因表達(dá)和蛋白質(zhì)生成。結(jié)論:急性肝衰竭時(shí)腸道菌落發(fā)生顯著改變,尤其在回腸部,布拉氏酵母菌可通過(guò)調(diào)節(jié)腸道菌群和抑制TGF-beta、Smad2、3、8的mRNA及蛋白質(zhì)表達(dá),從而緩解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.
【學(xué)位授予單位】:貴州醫(yī)科大學(xué)
【學(xué)位級(jí)別】:博士
【學(xué)位授予年份】:2017
【分類號(hào)】:R575.3
【參考文獻(xiàn)】
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