急性高血糖对小鼠主动脉基因表达谱扰动的可视化研究

发布时间：2018-12-31 09:42

【摘要】：目的:采用数据挖掘方法,基于Matlab平台对基因网络扰动可视化,以直观显示短时高血糖状态下动脉血管转录组改变。方法:在美国国立卫生研究中心(NCBI)GEO数据库下载数据集。利用Matlab将数据转化为计算机可识别的结构体,经过数据筛选,获得短时高血糖后表达模式扰动最明显的基因谱。利用三种聚类算法分析,基于DAVID进行基因本体学(GO)注释及富集分析,把相关通路标定在KEGG通路中,形成基因—表达谱系统分析。结果:经过对数据集的筛选、聚类将基因的变化模式归为9类,在该模型中有效地反应出短时高血糖对动脉血管的急性早期效应。GO富集分析显示,在急性炎症反应、心肌重构、维持细胞内钙离子稳态、细胞周期调控、细胞趋化作用等方面的基因显著富集;其中以与粘多糖、糖蛋白结构相关基因、脂肪分解代谢、肌原纤维组装相关基因显著富集。这些发现与以往研究的结论相吻合。K-均值聚类方法显示,在高血糖环境下基因表达上调,且不随血糖恢复正常表达的基因,主要有参与细胞周期调控、心肌重构、维持细胞内钙离子稳态的基因。结论:利用数据挖掘方法,实现急性高血糖对小鼠动脉基因表达谱波动模式的可视化描述,并为糖尿病的"代谢记忆"机制提供新的解释,即早期的高糖效应带来的动脉血管的不可逆的损伤,是导致冠心病患者降糖治疗无效的原因。即短暂的高糖水平的暴露可在分子水平上起到长久的影响。
[Abstract]:Aim: to visualize the disturbance of gene network based on Matlab platform in order to visualize the transcriptional changes of arterial vessels under the condition of short-term hyperglycemia. Methods: the data set was downloaded from the (NCBI) GEO database of the National Center for Health Research. Matlab was used to transform the data into a computer recognizable structure. After data screening, the gene profile with the most obvious disturbance of the expression pattern after short-term hyperglycemia was obtained. Three clustering algorithms were used to analyze the gene ontology (GO) annotation and enrichment based on DAVID. The related pathways were labeled in the KEGG pathway and the gene-expression profile system was analyzed. Results: after the data set was screened, the gene change patterns were classified into 9 groups, and the acute early effects of short-term hyperglycemia on arterial vessels were effectively reflected in the model. GO enrichment analysis showed that in acute inflammatory response, Myocardial remodeling, maintenance of intracellular calcium homeostasis, cell cycle regulation, and chemotaxis, etc. Among them, genes related to mucopolysaccharide, glycoprotein structure, fat catabolism and myofibrillar assembly were significantly enriched. These findings are consistent with previous studies. K- mean clustering method shows that genes that are up-regulated in hyperglycemia and do not return to normal with blood glucose are mainly involved in cell cycle regulation and myocardial remodeling. A gene that maintains intracellular calcium homeostasis. Conclusion: the data mining method is used to visualize the fluctuating pattern of gene expression profile in mice with acute hyperglycemia, and to provide a new explanation for the metabolic memory mechanism of diabetes mellitus. The irreversible damage of arterial vessels caused by early high glucose effect is the cause of ineffective hypoglycemic therapy in patients with coronary heart disease. Transient exposure to high glucose levels can have a lasting effect on the molecular level.
【作者单位】：北京协和医学院中国医学科学院国家心血管病中心阜外医院冠心病诊治中心;
【基金】：国家自然科学基金委员会面上项目(81670415)
【分类号】：R587.2

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