阿尔茨海默病患者外周血和脑组织GPI基因表达观察及其功能的生物信息学分析  

Observation of GPI gene expression and bioinformatics analysis of its function in peripheral blood and brain tissues of patients with Alzheimer's disease

作　　者：马国维 钟欣[1] 杜可[1] 宫世强 刘明妍[1] 魏敏杰[1] MA Guowei;ZHONG Xin;DU Ke;GONG Shiqiang;LIU Mingyan;WEI Minjie(College of Pharmacy,China Medical University,Shenyang 110122,China)

机构地区：[1]中国医科大学药学院,沈阳110122

出　　处：《山东医药》2018年第48期1-4,共4页Shandong Medical Journal

基　　金：国家自然科学基金资助项目(81501098;81703519;81803751);"重大新药创制"科技重大专项课题(2018ZX09711001-008-006);沈阳市科技创新"双百工程"项目(100040)

摘　　要：目的基于GEO芯片技术观察阿尔茨海默病(AD)患者外周血和脑组织磷酸葡萄糖异构酶(GPI)基因的表达情况,分析GPI基因的功能及其与AD发病的关系。方法获取健康老年人大脑额叶皮质样本18例份、颞叶皮质样本19例份、海马样本19例份、外周血样本14例份及AD患者大脑额叶皮质样本15例份、颞叶皮质样本10例份、海马样本29例份、外周血样本14例份。利用GEO数据库筛选适用于AD的相关芯片,检测健康老年人及AD患者外周血、脑组织样本GPI基因。借助蛋白-蛋白相互作用(PPI)网络图筛选GPI的相关基因;通过基因本体(GO)分析及京都基因和基因组百科全书(KEGG)功能富集分析,筛选GPI基因可能参与并主要影响的生物学功能或通路。结果外周血芯片分析结果显示,健康老年人中,女性外周血GPI基因表达量低于男性,且低于男性AD患者(P均<0. 05);相同性别人群中,AD患者外周血GPI基因表达量低于健康老年人(P均<0. 05)。脑组织芯片分析结果显示,AD患者海马组织GPI基因表达明显下调,低于额叶、颞叶皮质(P均<0. 05); GPI基因表达量随AD病情加重而持续减少(P均<0. 05)。通过PPI网络图,共筛选出10个与GPI高度相关基因,分别为PKM、TPI1、PFKL、PKLR、PGM1、PFKP、ENO3、PFKM、H6PD、TKT。GO分析及KEGG功能富集分析结果显示,GPI基因与其相关的10个基因在功能富集上与糖酵解、合成、分解、代谢等能量代谢过程高度相关。结论 AD患者外周血及海马组织GPI基因表达下调,随AD病情加重,其表达持续减少; GPI基因与其相关基因可能参与AD患者海马脑区能量代谢的功能调控。Objective The expression of glucose-6-phosphate isomerase(GPI)gene in peripheral blood and brain tissues of patients with Alzheimer′s disease(AD)was observed based on GEO chip technology,and the relationship between GPI function and the pathogenesis of AD was analyzed.Methods We obtained 18 cases of frontal cortex,19 cases of temporal cortex,19 cases of hippocampus,and 14 cases of peripheral blood samples from the healthy elderly.In the AD patients,15 cases of the frontal cortex of the brain,10 cases of the temporal cortex,29 cases of the hippocampus,and 14 cases of the peripheral blood samples were selected.The GEO database was used to screen the relevant chips for AD,and the GPI genes in peripheral blood samples and brain tissue samples of the healthy elderly and AD patients were detected.Screening out the genes related to GPI via protein-protein interaction(PPI)network map.Gene function enrichment analysis was performed by gene ontology(GO)analysis and we used the Kyoto Gene and Genomic Encyclopedia(KEGG)for the enrichment analysis and to screen out the biological functions or pathways in which GPI genes may be involved and primarily affected.Results Peripheral blood microarray analysis showed that the expression of GPI gene in the peripheral blood of females was lower than that in males,and was lower than that in male AD patients(P<0.05).In the same gender group,the expression of GPI gene in the peripheral blood of AD patients was lower than that in the healthy people(P<0.05).The results of brain tissue microarray analysis showed that the expression of GPI gene in the hippocampus of AD patients was significantly down-regulated,which was lower than that of the other brain regions(frontal and temporal cortex)and was not related to gender(P<0.05).The expression of GPI gene continued to decrease with the severity of AD(P<0.05).Ten highly GPI-related genes were screened out by PPI network map,including PKM,TPI1,PFKL,PKLR,PGM1,PFKP,ENO3,PFKM,H6PD,and TKT.GO analysis and KEGG functional enrichment analysis showed

关 键 词：阿尔茨海默病 磷酸葡萄糖异构酶 生物信息学分析 能量代谢 

分 类 号：R742[医药卫生—神经病学与精神病学]