急性高血糖对小鼠主动脉基因表达谱扰动的可视化研究  

Visualization Study on the Disturbance of Aorta Gene Expression Profile in Acute Hyperglycemia Mice Model

作　　者：张心月[1] 俞梦越[1] 

机构地区：[1]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,北京市100037

出　　处：《中国循环杂志》2017年第9期924-929,共6页Chinese Circulation Journal

基　　金：国家自然科学基金委员会面上项目(81670415)

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。Objective： Based on the visualization function for gene network disturbance of Matlab platform, data mining method was used to directly observe transcriptional changes in aorta vessel at short-time hyperglycemia condition. Methods： The information was down loaded from GEO database of NCBI. Using Matlab system to transfer the data set to a computer-readable structure, using data filter to obtain apparent gene expression disturbance profile after short-time hyperglycemia condition. Applying three clustering algorithms, based on DAVID platform to conduct gene ontology （GO） annotation and enrichment analysis in order to calibrate KEGG pathway and to form gene expression profile analysis. Results： Via data set screening, the pattern of gene expression was divided into 9 clusters by special algorithms. GO analysis indicated that obvious gene enrichments were found in acute inflammation reaction gene, myocardium remodeling gene, stabilizing intracellular calcium gene, cell cycle regulation gene, chemotactic effect gene; especially in mucopolysaccharide gene, glycoprotein structure related gene, fat catabolism gene and myofibril related gene. The above findings were identical to previous study. K-means clustering method presented that in hyperglycemia condition, up-regulated genes didn＇t return to normal level when blood glucose back to normal which mainly including cell cycle regulation gene, myocardium remodeling gene and stabilizing intracellular calcium gene. Conclusion： Our work provided a new explanation of diabetes metabolic memory; short-term hyperglycemia caused arterial damage was irreversible which incurred inefficient hypoglycemic therapy in coronary artery disease patients.

关 键 词：高血糖症 内皮细胞 基因表达谱 

分 类 号：R541[医药卫生—心血管疾病]