糖尿病肾脏疾病发生发展中程序性细胞死亡作用机制的研究  

The study on the mechanism of programmed cell death in the occurrence and development of diabetic kidney disease

作　　者：裴珍珍 张珊 周扬 陈玉鹏 常瑞婷 倪青[2] PEI Zhenzhen;ZHANG Shan;ZHOU Yang(The Graduate School of Beijing University of Chinese Medicine,Beijing 100105,China)

机构地区：[1]北京中医药大学研究生院,100105 [2]中国中医科学院广安门医院内分泌科

出　　处：《中国糖尿病杂志》2025年第1期28-35,共8页Chinese Journal of Diabetes

基　　金：国家自然科学基金(82174354)。

摘　　要：目的探讨程序性细胞死亡(PCD)对DKD发生发展的作用机制。方法检索基因表达综合数据库,获取数据集GSE30529和GSE30122,分析DKD差异表达基因(DEGs)。通过基因集富集分析网站、铁死亡数据库、自噬数据库并结合既往相关文献,分别获取凋亡、坏死性凋亡、焦亡、自噬和铁死亡相关基因,并与上述DKD差异基因交集,鉴定DKD差异表达的PCD相关基因。通过基因本体(GO)和京都基因与基因组百科全书(KEGG)通路富集,分析核心基因的生物学功能和潜在通路。采用蛋白质-蛋白质相互作用网络,分析目的基因的互作关系,并借助Cytoscape中Cyto Hubba插件筛选Hub基因。结果GSE30529数据集共获取460个DEGs,GSE30122数据集共获取992个DEGs,合并去重后共获取932个DEGs。对DEGs与PCD相关基因取交集,获取凋亡基因61个,坏死性凋亡基因7个,焦亡基因39个,自噬基因18个,铁死亡基因16个。KEGG显示,与PCD中凋亡、坏死性凋亡、焦亡和自噬相关的DEGs富集通路主要为糖基化终末产物-糖基化终末产物受体(AGE-RAGE)、IL-17、核因子κB(NF-κB)、TNF信号通路,与铁死亡相关的DEGs富集通路主要为脂肪酸降解通路。GO富集显示,DKD中差异表达的PCD相关基因的生物学过程主要涉及对NF-κB诱导激酶/NF-κB、IL-1、IL-17等信号的调控。结论DKD中差异表达的PCD相关基因,主要富集在AGE-RAGE、IL-17、NF-κB、TNF等相关的信号通路中,PCD在DKD发病中的关键作用。Objective To discuss the potential mechanisms by which programmed cell death(PCD) might contribute to the pathogenesis of diabetic kidney disease(DKD). Methods Retrieve the datasets GSE30529 and GSE30122 from the Gene Expression Omnibus database and analyze them to obtain differentially expressed genes(DEGs) associated with DKD. Utilize the Gene Set Enrichment Analysis website,the ferroptosis database,and the autophagy database,along with relevant literature,to identify genes associated with apoptosis,necroptosis,pyroptosis,autophagy,and ferroptosis. Cross-reference these genes with the DKD DEGs to identify PCD-related genes that are differentially expressed in DKD. Perform Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analyses to explore the biological functions and potential pathways of the core genes. Conduct a protein-protein interaction network analysis to examine the interaction relationships of the target genes,and use the CytoHubba plugin in Cytoscape to screen for Hub genes. Results In the GSE30529 dataset,a total of 460 DEGs were identified,while the GSE30122 dataset yielded 992 DEGs. After merging and removing duplicates,932 DEGs were obtained. By intersecting these DEGs with PCD-related genes,61 apoptosis-related genes,7 necroptosis-related genes,39 pyroptosis-related genes,18 autophagy-related genes,and 16 ferroptosis-related genes associated with DKD were identified. The KEGG analysis results indicated that the DEGs related to apoptosis,necroptosis,pyroptosis,and autophagy in PCD were primarily enriched in pathways associated with diabetic complications,including the AGE-RAGE,IL-17,NF-κB,and TNF signaling pathways. In contrast,DEGs related to ferroptosis were mainly enriched in the fatty acid degradation pathway. GO enrichment analysis revealed that the biological processes of the differentially expressed PCD related genes in DKD were primarily involved in the regulation of signals such as NF-κB-inducing kinase/NF-κB,IL-1,and IL-17.Conclusions Differential

关 键 词：糖尿病肾脏疾病 程序性细胞死亡 基因表达综合数据库 生物信息学 

分 类 号：R692.9[医药卫生—泌尿科学] R587.2[医药卫生—外科学]