2型糖尿病发病与高密度脂蛋白关系的机制研究  

A mechanism study on the association of type 2 diabetes and high-density lipoprotein

作　　者：唐博 邵静 崔静 孙健平[1,4] TANG Bo;SHAO Jing;CUI Jing;SUN Jianping(Nutrition and Food Hygiene,School of Public Health,Qingdao University,Qingdao 266021,Shandong,China;Department of Otolaryngology,People's Hospital of Pingyi County,Linyi 273300,Shandong,China;Family Planning Service Center for Maternal and Child Health in Licang District,Qingdao 266041,Shandong,China;Qingdao Municipal Center for Disease Control and Prevention,Qingdao Institute of Preventive Medicine,Qingdao 266033,Shandong,China)

机构地区：[1]青岛大学公共卫生学院营养与食品卫生学,山东青岛266021 [2]平邑县人民医院耳鼻喉科,山东平邑273300 [3]青岛市李沧区妇幼保健计划生育服务中心,山东青岛266041 [4]青岛市疾病预防控制中心/青岛市预防医学研究院,山东青岛266033

出　　处：《山东大学学报（医学版）》2020年第3期99-106,共8页Journal of Shandong University:Health Sciences

基　　金：青岛糖尿病预防项目(WDF05-108、WDF07-308);青岛市科技局立项(19-6-1-5-nsh);青岛市2017年度医药科研指导计划(2017-WJZD134);青岛市医疗卫生优秀人才培养项目。

摘　　要：目的 探讨2型糖尿病(T2DM)发病与高密度脂蛋白(HDL)的内在分子生物学机制.方法 采用分子信息学方法,借助GEO Datasets数据库与比较毒理基因组学数据库(CTD),分别获取T2DM与HDL关联的基因,并筛选出二者共同的差异表达基因(DEGs).采用DAVID在线软件,对T2DM与HDL关联的共同DEGs进行基因本体论(GO)分析和KEGG信号通路等基因富集分析;采用String在线软件和Cytoscape的插件MCODE,对T2DM与HDL关联的共同DEGs进行蛋白互作(PPI)网络分析.结果 GEO与CTD数据库分析显示,T2DM与HDL关联的有13个DEGs;GO分析表明,T2DM与HDL共同DEGs参与了胆固醇代谢过程等生物学进程;KEGG信号通路富集结果表明,T2DM与HDL共同DEGs参与了HIF-1信号通路、Toll样受体信号通路、cGMP-PKG信号通路等;PPI分析结果显示,T2DM与HDL关联的13个DEGs均参与了网路构建,该蛋白网络共有27条边,平均蛋白节点度为4.15,局部聚类系数为0.74,蛋白相互作用网络具有统计学差异(P<0.001),T2DM与HDL相关的蛋白网络由LEPR、MAPK3、AKT1、NOS3、APOE和SCARB1等6个节点蛋白组成.结论 T2DM发病主要通过胆固醇代谢过程、HIF-1信号通路、Toll样受体信号通路、cGMP-PKG信号通路等与HDL异常关联,可能的因果关联尚需进一步研究.Objective To explore the molecular mechanism of type 2 diabetes(T2DM)and high-density lipoprotein(HDL)by bioinformatics.Methods Genes of T2DM and HDL were obtained from GEO database and Comparative Toxicogenomics Database(CTD)to screen the same differentially expressed genes(DEGs).Gene function enrichment analysis of gene ontology(GO)and KEGG pathway in DEGs were analyzed with DAVID online software.Protein-pro-tein interaction(PPI)network about DEGs was analyzed with String online software and MCODE of Cytoscape.Results There were 13 DEGs associated with T2DM and HDL,which played a role in cholesterol metabolic process.The DEGs were involved in HIF-1 signaling pathway,Toll-like receptor signaling pathway and cGMP-PKG signaling pathway.All 13 DEGs were involved in the PPI network,which had 27 edges,with average protein node degree of 4.15 and local clustering coefficient of 0.74.The PPI network had a significant difference(P<0.001).The PPI network asso-ciated with T2DM and HDL was composed of 6 node proteins,including LEPR,MAPK3,AKT1,NOS3,APOE and SCARB1.Conclusion The pathogenesis of T2DM involves abnormal HDL through cholesterol metabolic process,HIF-1 signaling pathway,Toll-like receptor signaling pathway and cGMP-PKG signaling pathway.Further studies are needed to clarify the possible causal association between lipid and T2DM.

关 键 词：2型糖尿病 高密度脂蛋白 基因本体学论分析 KEGG分析 蛋白互作网络分析 

分 类 号：R587.1[医药卫生—内分泌]