基于生物信息学分析急性肾损伤关键基因及靶向中药筛选  

Key genes and targeted traditional Chinese medicine screening for acute kidney injury based upon bioinformatics

作　　者：叶海婷 杨定平[1] 李鹏艳 Ye Hai-ting;Yang Ding-ping;Li Peng-yan(Department of Nephrology,Renmin Hospital,Wuhan University,Wuhan 430060,China;Department of Blood Transfusion,Third Municipal Hospital,Wuhan 430060,China)

机构地区：[1]武汉大学人民医院肾病内科,武汉430060 [2]武汉市第三医院输血科,武汉430060

出　　处：《临床肾脏病杂志》2024年第8期667-676,共10页Journal Of Clinical Nephrology

基　　金：国家自然科学基金(81670631)。

摘　　要：目的为深入了解急性肾损伤(acute kidney injury,AKI)发生的分子机制和探索AKI的中药防治策略,本研究利用生物信息学方法分析了AKI的关键基因,并预测了具有防治作用的中药。方法从基因表达综合数据库(gene expression omnibus database,GEO)下载AKI基因芯片数据集GSE30718并利用GEO2R在线工具分析,同时从比较毒理基因组学数据库(comparative toxicogenomics database,CTD)下载AKI的作用靶点,取二者交集即为AKI的差异表达基因(differential expression genes,DEGs);对DEGs进行富集分析和蛋白质相互作用分析,并运用Cytoscape软件计算关键基因;然后利用医学信息检索平台(Coremine Medical)检索关键基因对应的中药,统计出现频次最高的中药,再利用BATMAN-TCM数据库进一步分析其治疗AKI的分子机制。结果该研究共获得了206个DEGs,生物学功能富集分析提示这些DEGs主要与细胞外基质、免疫炎症反应和转录调控有关;FN1、ALB、COL1A1 JUN、TGFB1、FOS、PXDN、COL1A2、EGF、TIMP1是AKI的关键基因,由此获得可能用于治疗AKI的中药有丹参、人参、当归、三七等;其中以丹参出现频次最高,其治疗AKI的主要信号通路为磷脂酰肌醇3激酶/蛋白激酶B信号通路。结论本研究利用生物信息学工具和方法初步筛选了参与AKI的10个关键基因以及相关防治中药,并具体分析了丹参治疗AKI的分子机制,为AKI的临床治疗提供了新思路,也为后续科研提供了理论依据。Objective To gain a deeper understanding of molecular mechanisms underlying acute kidney injury(AKI),explore traditional Chinese medicine strategies for managing AKI,employ bioinformatics to analyze key genes associated with AKI and predict potential Chinese herbal medicines with therapeutic effects.Methods The AKI gene expression microarray dataset GSE30718 were downloaded from the database of Gene Expression Omnibus(GEO)and GEO2R online tool was utilized for analysis.Simultaneously,AKI target genes were obtained from the Comparative Toxicogenomics Database(CTD)and the intersection of these datasets yielded the differential expression genes(DEGs)associated with AKI.Enrichment analysis and protein-protein interaction analysis were performed on DEGs.Cytoscape software was employed for identifying key genes.Subsequently,a medical information retrieval platform(Coremine Medical)was utilized for searching for traditional Chinese medicines corresponding to these key genes with the most frequently occurring ones identified. Then the database of BATMANTCMwas employed for detailed analysis of molecular mechanisms involved in their therapeutic effectson AKI. Results For 206 DEGs, functional enrichment analysis confirmed their involvements inextracellular matrix regulation, immune-inflammatory responses and transcriptional regulation. FN1, Alb,COL1A1, JUN, TGFB1, FOS, PXDN, COL1A2, EGF and TIMP1 were identified as key genes forAKI. The potential traditional Chinese medicines for treating AKI included Danshen (Salvia Miltiorrhiza),Renshen (Radix Ginseng), Danggui (Angelica Sinensis) and Sanqi (Radix Notoginseng). AndDanshen had the highest frequency. The primary signaling pathway associated with Danshen's therapeuticeffects on AKI was signaling pathway of phosphatidylinositide 3-kinase/protein kinase B (PI3K/AKT).Conclusion This study has identified 10 key genes involved in AKI and their associated traditional Chinesemedicines. Specific analysis of Danshen's molecular mechanisms in treating AKI provides new insightsfor clin

关 键 词：急性肾损伤 生物信息学 关键基因 中药治疗 

分 类 号：R277.5[医药卫生—中医学]