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临床证据显示高果糖摄取与代谢综合征现象产生有高度相关性,然而关于母体在怀孕与哺乳期高果糖摄取对子代代谢综合征的发育程序化影响的研究却相对缺乏。本研究利用第二代测序(next-generation sequencing)技术分析母鼠高果糖摄取对新生第一天、离乳后一天(出生后三周)、以及成年期(出生后三个月)子代大鼠脑部、心脏、肾脏与膀胱四个器官转录组的影响。结果显示:(1)母鼠在怀孕与哺乳期高果糖摄取,会程序化胎鼠使其于成年期产生代谢综合征;(2)同时,在仔鼠脑部、心脏、肾脏与膀胱四个器官引起不同程度的转录组变化;(3)在新生第一天子代大鼠,有两个基因,分别是Errfi1与Ctgf,同时在四个器官中表现受到影响,此现象在子代离乳与成年期则消失;(4)参与果糖代谢、糖酵解及糖异生、脂肪代谢、以及胰岛素信号传导通路的基因转录也受到不同程度影响,此现象在新生第一天尤为显著。该结果提示,可利用第二代测序技术寻找不同年龄层子代器官特异性受母体高果糖摄取影响的基因转录变化,进而研发代谢综合征发育程序化在不同器官引起病变的可能机制与治疗策略。
Clinical evidence shows that there is a high correlation between high fructose intake and metabolic syndrome. However, studies on the influence of high fructose intake during pregnancy and lactation on the developmental programmedness of metabolic syndrome in offspring are relatively scarce. In this study, we used next-generation sequencing to analyze the effects of high fructose intake on the first day of newborn, one day after weaning (three weeks after birth), and the adult offspring (three months after birth) Effects of transcriptome of four organs of brain, heart, kidney and bladder in rats. The results showed that: (1) The female rats were ingested with high fructose during pregnancy and lactation, which would lead to programmed metabolic syndrome in adulthood. (2) In the meantime, in the brains, hearts, kidneys and bladder (3) On the first day of newborn offspring rats, there are two genes, Errfi1 and Ctgf, respectively, and their expression in four organs are affected at the same time. And adulthood disappeared. (4) The transcription of genes involved in fructose metabolism, glycolysis, gluconeogenesis, fat metabolism, and insulin signaling pathway were also affected to varying degrees, especially on the first day of newborn. The results suggest that the second generation sequencing technology can be used to search for the transcriptional changes of the organ-specific genes affected by the high fructose uptake in different age groups, and then to develop possible mechanism and treatment strategies for the development of metabolic syndrome in different organs .