基于生物信息学及分子对接技术探究羌活胜湿汤治疗强直性脊柱炎的作用机制  

The Mechanism of Qianghuo Shengshi Tang in the Treatment of Ankylosing Spondylitis Based on Bioinformatics and Molecular Docking Technology

作　　者：李金政 霍凤蕾 李志超[3] 邱红明[4] LI Jinzheng;HUO Fenglei;LI Zhichao;QIU Hongming(TCM school Shandong University of Traditional Chinese Medicine,Jinan 250014,China;Shandong University,Jinan 250100,China;Shandong University of Traditional Chinese Medicine,Jinan 250355,China;Affiliated Hospital to Shandong University of Traditional Chinese Medicine,Jinan 250000,China)

机构地区：[1]山东中医药大学中医学院,山东济南250014 [2]山东大学,山东济南250100 [3]山东中医药大学,山东济南250355 [4]山东中医药大学附属医院,山东济南250000

出　　处：《西部中医药》2023年第2期72-79,共8页Western Journal of Traditional Chinese Medicine

基　　金：国家自然科学基金(81473709);曹贻训全国名老中医传承工作室建设项目(国中医药人教函[2018]134号)。

摘　　要：目的:利用生物信息学及分子对接技术探究羌活胜湿汤治疗强直性脊柱炎的作用机制。方法:通过美国国家生物技术信息中心数据库(national center for biotechnology information,NCBI)、高通量基因表达数据库(gene expression omnibus,GEO)等数据库检索强直性脊柱炎相关芯片,利用R语言分析得到差异表达基因。借助人类基因数据库(GeneCards)、疾病基因数据库(DisGeNET)、孟德尔遗传综合数据库(online Mendelian inheritance in man,OMIM)、疾病数据库(MalaCards)、遗传药理学和药物基因组学数据库(pharmacogenetics and pharmacogenomics knowledge base,PharmGKB)等数据库对强直性脊柱炎已知靶基因进行检索与筛选,与差异表达基因去重取并集,对强直性脊柱炎的疾病靶基因进行预测。运用中药药理学平台(traditional chinese medicine systems pharmacology database and analysis platform,TCMSP)数据库对羌活胜湿汤七味中药的主要有效成分及作用靶基因进行筛选和挖掘,构建药物与疾病映射靶基因的蛋白质互作(protein-protein interaction,PPI)网络,通过基因注释(database for annotation,visualization and integrated discovery,David)数据库对药物-疾病关键靶基因进行生物通路及富集分析。最终将羌活胜湿汤中主要有效成分与关键靶基因进行分子对接。结果:羌活胜湿汤有效成分-靶基因网络图包含176个有效成分,相对应靶点137个;GEO数据库获得差异表达基因704个,通过疾病数据库检索与强直性脊柱炎发生发展相关的已知疾病靶标1323个,合并去重后共获得1950个已知疾病靶基因;最终获得映射靶基因46个,关键靶基因13个。羌活胜湿汤主要通过肿瘤坏死因子α(tumor necrosis factor-α,TNF-α)、白细胞介素6(interleukin-6,IL-6)、白细胞介素1β(interleukin-1β,IL-1β)、血管内皮生长因子A(vascular endothelial growth factor A,VEGFA)、氯霉素乙酰转移酶基因(chloramphnicol acetyltransferase,CAT)、雌激�Objective: To explore the mechanism of Qianghuo Shengshi Tang in the treatment of ankylosing spondylitis(AS) based on bioinformatics and molecular docking technology. Methods: The related chips of AS were retrieved from NCBI and GEO, differentially expressed genes(DGEs) were analyzed and obtained by using R language. The known target genes of AS were searched and screened via GeneCards, DisGeNET, OMIM,MalaCards and PharmGKB, and the target genes were predicted through taking the union set after removing the duplicate. The main active ingredients and the target genes of seven herbs contained in Qianghuo Shengshi Tang were screened and unearthed by using TCMSP, to construct PPI of medicine and disease mapping target genes,biological pathways and enrichment analysis of medicine and disease mapping target gene were conducted by using David. Consequently the main active components of Qianghuo Shengshi Tang were interlinked with key targets genes. Results: Network chart of active ingredients-target genes of Qianghuo Shengshi Tang contained 176 active ingredients, 137 corresponding targets;704 DGEs were obtained from GEO database, and 1323 known disease targets related to the incidence and development of AS were searched from disease database, and 1950 known disease target genes were gained after merging and removing the duplicate;finally, 46 mapping target genes and 13 key target genes were yielded. Qianghuo Shengshi Tang mainly acts on lipopolysaccharide-mediated signaling pathway, positive regulation of nitric oxide biosynthesis, biological processes such as angiogenesis, Fox0 signaling pathway, inflammatory bowel disease, and many signaling pathways including the ones related to proinflammatory factors through TNF-α, IL-6, IL-1β, VEGFA, CAT, ESR1 and PTGS2. The results of molecular docking displayed that the main active components of Qianghuo Shengshi Tang entered the active sites in the process of docking with key targets genes, showing the strongest combining capacity. Conclusion: The potential mechanism of Qian

关 键 词：强直性脊柱炎 羌活胜湿汤 生物信息学 差异基因 分子对接 机制 

分 类 号：R593.23[医药卫生—内科学]