摘要
目的利用生物信息学技术筛选阿尔茨海默病(AD)不同脑区差异表达基因,探讨各脑区的免疫机制,以预测潜在的治疗中药。方法从GEO数据库获得AD的样本数据,进行差异表达基因(DEGs)分析及加权基因共表达网络分析(WGCNA),对各脑区最相关的模块进行蛋白质-蛋白质相互作用(PPI)网络分析获得核心基因,并使用受试者工作特征曲线(ROC)曲线评估其诊断价值。对差异基因进行免疫通路富集分析,并使用CIBERSORT算法分析免疫细胞浸润模式,通过Coremine Medical筛选治疗AD的潜在中药。结果大脑的内嗅皮层(EC)区有3280个差异基因、海马体(HIP)区有1591个差异基因、内侧颞回(MTG)区有3995个差异基因、后扣带(PC)区有2056个差异基因、额上回(SFG)区有907个差异基因、初级视觉皮层(VCX)区有1480个差异基。其中EC与VCX区与blue模块相关性高、HIP与PC区与turquoise模块相关性高、MTG、SFG别与绿色和黄色模块相关性高。PPI网络显示EC区有4个Hub基因,HIP区有13个Hub基因,MTG区有4个Hub基因,PC区有9个Hub基因,SFG区有17个Hub基因,VCX区有13个Hub基因。不同脑区富集有不同免疫通路的模块。通过基因映射到姜黄为治疗AD的潜在中药,其映射到EP300、PPARG、CCND1、GSK3B、BCL2、EGFR、KDR、MYC和IL1B等基因上。结论AD患者在不同脑区表现出多样化的免疫途径,这种差异与AD发病机制紧密相连。姜黄有望作为治疗AD的潜在中药。
Objective To identify differentially expressed genes(DEGs)in different brain regions of Alzheimer's disease(AD)using bioinformatics techniques,explore the immune mechanisms in each brain region,and predict potential therapeutic drugs.Methods AD sample data were obtained from the GEO database,and DEGs analysis and weighted gene co-expression network analysis(WGCNA)were performed on each brain region.The core genes in the most related modules were obtained by protein-protein interaction(PPI)network analysis,and their diagnostic value was evaluated by ROC curve.Differential genes were subjected to immune pathway enrichment analysis,and immune cell infiltration patterns were analyzed using CIBERSORT algorithm.Potential therapeutic drugs for AD were screened using Coremine Medical.Results A total of 3280 differential genes were identified in the EC region,1591 in the HIP region,3995 in the MTG region,2056 in the PC region,907 in the SFG region,and 1480 in the VCX region.EC and VCX were highly related to the blue module,HIP and PC were highly related to the turquoise module,and MTG and SFG were highly related to the green and yellow modules.The PPI network showed that there were four Hub genes in the EC region,13 in the HIP region,four in the MTG region,nine in the PC region,and 17 in the SFG region.Different brain regions were enriched with different immune pathway modules.Subsequently,Curcumae Longae Rhizoma was identified as a potential traditional Chinese medicine(TCM)for AD treatment based on its association with key genes such as EP300,PPARG,CND1,GSK3B,BCL2,EGFR,KDR,MYC,and IL1B.Conclusion AD patients exhibit diverse immune pathways across distinct brain regions,and this disparity is intricately associated with the pathogenesis of AD.Curcumae Longae Rhizoma holds promising potential as a Chinese medicinal intervention for the treatment of AD.
作者
宋晓娜
高耀
王晓堂
陈文璐
闫晓如
范炤
宋国华
SONG Xiaona;GAO Yao;WANG Xiaotang;CHEN Wenlu;YAN Xiaoru;FAN Zhao;SONGGuohua(School of Basic Medical Sciences,Shanxi Medical University,Taiyuan 030001,China;Laboratory Animal Center,Shanxi Medical University,Taiyuan 030001,China;Translational Medicine Research Center,Shanxi Medical University,Taiyuan 030001,China;Department of Psychiatry,First Hospital/First Clinical Medical College of Shanxi Medical University,Taiyuan 030001,China)
出处
《药物评价研究》
CAS
北大核心
2024年第7期1520-1528,共9页
Drug Evaluation Research
基金
山西省科技创新人才团队项目(202204051002032)
山西省中医药管理局资助项目(2023ZYYC2034)
山西省卫健委卫生健康科研课题(2021031)。
关键词
阿尔茨海默病
生物信息学
中药筛选
免疫细胞浸润
姜黄
Alzheimer's disease
bioinformatics
screening of traditional Chinese medicines
immune cell infiltration
Curcumae Longae Rhizoma
