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The effects of betaine treatment on rats fed an acute bolus of ethanol at 3 and 12 h post bolus: a microarray analysis

机译:甜菜碱治疗对大剂量推注后3小时和12小时喂食乙醇的大鼠的影响:微阵列分析

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摘要

Betaine, a methyl donor active in methionine metabolism, is effective in preventing and reversing experimental alcohol liver disease. The metabolic and molecular biologic mechanisms involved in this prevention are only partially known. To further investigate how betaine modifies the effects of ethanol on the liver, rats were given an acute ethanol bolus with or without betaine and the results were compared to isocaloric dextrose-fed controls. Livers were subjected to microarray analysis, and functional pathways and individual gene expression changes were analyzed. Experimental groups were compared by Venn diagrams showing that both ethanol and betaine caused a change in the expression of a large number of genes indicating that the changes were global. The bio-informatic analysis showed that all the KEGG functional pathways were affected and mainly down regulated at 3 h post bolus when ethanol plus betaine were compared with ethanol-fed rats. The most profound effect of betaine was on the metabolic pathways both at 3 and 12 h post bolus. At 3 h, the changes in gene expression were mostly down regulated, but at 12 h, the changes were regulated equally up and down. This hypothesis-driven analysis showed that the effects of betaine on the effects of ethanol were partly transient.
机译:甜菜碱是一种在蛋氨酸代谢中活跃的甲基供体,可有效预防和逆转实验性酒精性肝病。涉及该预防的代谢和分子生物学机制仅是部分已知的。为了进一步研究甜菜碱如何改变乙醇对肝脏的影响,在有或没有甜菜碱的情况下给大鼠急性乙醇推注,并将结果与​​等热量葡萄糖喂养的对照组进行比较。对肝进行微阵列分析,并分析功能途径和单个基因表达变化。实验组通过维恩图进行比较,表明乙醇和甜菜碱都引起大量基因表达的改变,表明这些改变是全球性的。生物信息学分析表明,当将乙醇加甜菜碱与以乙醇喂养的大鼠进行比较时,在推注后3小时,所有KEGG功能途径均受到影响,并且主要被下调。甜菜碱最深远的影响是在推注后3和12 h对代谢途径的影响。在3小时,基因表达的变化大部分被下调,但在12小时,基因表达的变化被上调和下调。该假设驱动的分析表明,甜菜碱对乙醇的影响部分是暂时的。

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