摘要
目的探究经典中药配伍组合黄芪-当归药对(芪归药对)对糖尿病合并心血管并发症的治疗作用及分子机制。方法运用BATMAN数据库对芪归药对进行分析,检索GEO数据库中关于糖尿病合并心血管并发症的相关基因芯片数据,借助GEO2R分析差异基因,构建靶点互作关系网络,拓扑得到芪归药对治疗糖尿病心血管并发症的关键基因;运用DAVID数据库对关键基因进行基因本体功能和KEGG通路富集分析。将20只SD大鼠随机分为健康对照组、糖尿病合并心血管并发症模型组、阳性对照二甲双胍治疗组和芪归药对治疗组,每组5只;除健康对照组外,其余各组均给予高脂高糖饲料并建立糖尿病合并心血管并发症模型;观察各组大鼠心肌细胞中PI3K、Akt3蛋白的表达情况。结果(1)在BATMAN数据库中分析得到芪归药对的相关靶点基因1332个,在GEO数据库中检索得到3个糖尿病合并心血管病变的芯片数据文件(GSE26887、GSE43950、GSE46262),利用GEO2R分析筛选出2759个差异基因;经映射得到芪归药对治疗糖尿病合并心血管并发症的关键基因247个。(2)通过STRING数据库构建关键靶点的差异蛋白相互作用(PPI)网络图,运用Cytoscape 3.7.2构建“芪归药对—活性成分—靶点”网络。采用DAVID数据库进行功能富集分析提示,芪归药对治疗糖尿病合并心血管并发症的生物学进程主要集中在RNA聚合酶Ⅱ启动子转录的正负调控、氧化还原过程、信号转导、凋亡过程、炎症反应、细胞增殖的正调控等,信号通路涉及新陈代谢通路、癌症通路、肿瘤坏死因子(TNF)信号通路、5'-单磷酸(cAMP)信号通路、环磷酸鸟苷酸-蛋白激酶(cGMP-PKG)信号通路、磷脂酰肌醇3-激酶与丝氨酸/苏氨酸激酶(PI3K-Akt)信号通路、非酒精性脂肪肝通路、胰岛素抵抗通路等。(3)采用SD大鼠的动物模型实验结果显示,与健康对照组比较,未接受治疗的糖尿病合并心血管
Objective To explore the molecular mechanism of a classic traditional Chinese medicine compatibility combination of Astragalus membranaceus(A.m)and Angelica sinensis(A.s)in treatment of diabetes mellitus with cardiovascular complications.Methods The BATMAN database was used to analyze A.m and A.s respectively.The chips data related to diabetes mellitus with cardiovascular complications were retrieved from GEO database.The differential genes were analyzed by GEO2R to construct the protein-protein interaction(PPI)network,and the key target genes of A.m-A.s were obtained by topology,and DAVID database was used for gene ontology(GO)and KEGG pathway enrichment analysis of key genes.A total of 20 SD rats were randomly divided into healthy control group,diabetes mellitus complicated with cardiovascular complications group,metformin group,and A.m-A.s group(5 each).All the rats except those in HC group were fed with high fat and high sugar feeds,and used to establish the model of diabetes mellitus with cardiovascular complications.The expressions of PI3K and Akt3 in cardiomyocytes of the rats in each group were observed.Results(1)A total of 1332 target genes related to A.m-A.s combination were analysis obtained from BATMAN database,and 3 chip data files related to diabetes with cardiovascular diseases(GSE26887,GSE43950 and GSE46262)were retrieved from GEO database including 2759 differential genes screened by GEO2R analysis and 247 key genes of A.m-A.s combination in treatment of diabetes mellitus with cardiovascular complications.(2)The protein-protein interaction(PPI)network diagram of key targets was constructed by STRING database,and the"A.m-A.s-active ingredients-targets"network was constructed by Cytoscape 3.7.2.The functional enrichment analysis with DAVID database showed that the biological process of A.m-A.s in treatment of diabetes mellitus and cardiovascular complications was mainly concentrated in positive and negative regulation of RNA polymerase II promoter transcription,redox process,signal transduction,apo
作者
董又滋
赵泉霖
王毓国
Dong You-Zi;Zhao Quan-Lin;Wang Yu-Guo(The First Clinical Medical College of Shandong University of Traditional Chinese Medicine,Jinan,Shandong 250014,China;Department of General Internal Medicine,the Affiliated Hospital of Shandong University of Traditional Chinese Medicine,Jinan,Shandong 250014,China;Department of Traditional Chinese Medicine,the Sixth Medical Center of Chinese PLA General Hospital,Beijing 100142,China)
出处
《解放军医学杂志》
CAS
CSCD
北大核心
2022年第12期1190-1200,共11页
Medical Journal of Chinese People's Liberation Army
基金
国家自然科学基金(81774254)
山东省自然科学基金(ZR2021MH275)。
关键词
糖尿病合并心血管并发症
黄芪-当归
GEO数据库
生物信息学
diabetes mellitus with cardiovascular complications
Astragalus membranaceus and Angelica sinensis
GEO database
bioinformatics
