基于生物信息学和分子对接技术探讨阔叶十大功劳调节免疫干预糖尿病视网膜病变的研究  

Mechanism of Mahonia bealei(Fort.)Carr.regulating immunity in diabetic retinopathy based on bioinformatics and molecular docking

作　　者：张楠楠 姜运会 杨凯平 李军 ZHANG Nannan;JIANG Yunhui;YANG Kaiping;LI Jun(School of Basic Medical Sciences,Guizhou University of Traditional Chinese Medicine,Guiyang 550025,China;School of Pharmacy,Guizhou University of Traditional Chinese Medicine,Guiyang 550025,China)

机构地区：[1]贵州中医药大学基础医学院,贵州贵阳550025 [2]贵州中医药大学药学院,贵州贵阳550025

出　　处：《贵州科学》2024年第2期5-13,共9页Guizhou Science

基　　金：贵州省卫生健康委科学技术基金,项目编号:gzwkj2023-266;贵州中医药大学博士启动基金,项目编号:〔2021〕10号。

摘　　要：目的:基于生物信息学和分子对接技术探讨糖尿病视网膜病变(Diabetic Retinopathy,DR)、免疫与阔叶十大功劳之间的关系。方法:通过文献、Symmap、Swisstarget和TCMSP数据库获取十大功劳的靶点;从GEO获取GSE53257、GSE60436基因芯片数据集,并应用GEO2R工具进行数据预处理,使用R软件包stats对数据进行PCA分析评估,使用R语言CIBERSORT包进行免疫浸润和WGCNA分析;将数据集得到的差异表达基因、十大功劳靶点和WGCNA获得的免疫相关基因取交集;利用GeneMANIA数据库预测交集靶点相关的基因并构建关键基因的相互作用网络图,并借助于DAVID数据库对交集基因进行GO功能注释与KEGG通路富集分析;最后进行分子对接,明确得出十大功劳发挥作用的主要化合物。结果:获得Hub genes 8个(CDK2、CDK1、CHEK1、TP53、CDK6、CCND1、TYMS和CDC45),KEGG主要富集在黑色素瘤、胶质瘤和cAMP信号通路;通过分子对接发现其中7个Hub genes(CDK6、CHEK1、CDK2、CDK1、CCNA2、TP53、TYMS)的蛋白可以与十大功劳中的槲皮素、杜鹃花素、小檗碱、异鼠李素等11种化合物进行良好的结合。结论:本研究通过生物信息学和分子对接技术初步阐释了免疫、十大功劳与DR三者之间的关系,为十大功劳治疗DR的临床应用提供理论依据。This study explored the relationship between Diabetic Retinopathy(DR),Immunity and Mahonia bealei(Fort.)Carr.based on bioinformatics and molecular docking.The targets of Mahonia bealei were obtained from literature and Symmap,Swisstarget and TCMSP databases.the GSE53257 and GSE60436 gene microarray datasets were obtained from GEO,and the GEO2R tool was applied to pre-process the data.The data was evaluated by PCA analysis using the R package stats,and the R language CIBERSORT package was used for immune infiltration and WGCNA analysis.The differentially expressed genes obtained from the dataset,the targets of Mahonia bealei,and the immune-related genes obtained by WGCNA were intersected.The GeneMANIA database was used to predict the genes related to the intersection targets and construct the interaction network map of the key genes.GO functional annotation and KEGG pathway enrichment of the intersection genes were performed with the help of DAVID database.Finally,molecular docking was performed to clarify the main active compounds in Mahonia bealei.Eight Hub genes(CDK2、CDK1、CHEK1、TP53、CDK6、CCND1、TYMS and CDC45)were obtained.KEGG was mainly enriched in melanoma,glioma and cAMP signaling pathways.The proteins of seven of the Hub genes(CDK6,CHEK1,CDK2,CDK1,CCND1,TP53 and TYMS)were found to bind well to 11 compounds(quercetin,rhodopsin,berberine,isorhamnetin,etc.)in Mahonia bealei by molecular docking.This study initially elucidated the relationship between immunity,Mahonia bealei and DR through bioinformatics and molecular docking,and provided a theoretical basis for the clinical application of Mahonia bealei in the treatment of DR.

关 键 词：糖尿病视网膜病变 免疫 阔叶十大功劳 

分 类 号：R285[医药卫生—中药学]