基于网络药理学和分子对接探究益肾达络饮治疗多发性硬化的作用机制  

Molecular Mechanism of Yishen Daluo Decoction in treatment of Multiple Sclerosis Based on Network Pharmacology and Molecular Docking

作　　者：任嘉彦 丁文婧 王忠敏 何静文 尚晓玲[1] REN Jiayan;DING Wenjing;WANG Zhongmin;HE Jingwen;SHANG Xiaoling(Changchun University of Chinese medicine,Changchun 130117,China)

机构地区：[1]长春中医药大学,长春130117

出　　处：《中国中医基础医学杂志》2022年第12期2026-2034,2070,共10页JOURNAL OF BASIC CHINESE MEDICINE

基　　金：国家自然科学基金(81873216)-基于组蛋白乙酰化探讨益肾解毒通络法对EAE小鼠星形胶质细胞微环境影响机制的研究。

摘　　要：目的 利用网络药理学方法研究益肾达络饮治疗多发性硬化(multiple sclerosis, MS)的作用机制,并对所得靶点通路进行验证。方法 应用TCMSP数据库和GeneCards、OMIM、PharmGkb、TTD、Drugbank数据库获取益肾达络饮的活性成分、靶点和多发性硬化的靶点并取交集获得潜在治疗靶点。利用Cytoscape3.8.0、STRING、CytoNCA、R软件,得到活性成分-靶点基因网络和PPI网络、GO、KEGG富集分析结果,在此基础上进行分子对接验证和体外实验验证。通过提取乳鼠原代星形胶质细胞,脂多糖(lipopolysaccharide, LPS)造成多发性硬化中枢炎症环境模型,CCK-8法检测细胞的存活率,ELISA法检测肿瘤坏死因子(tumor necrosis factor, TNF)α、白细胞介素(interleukin, IL)1β关键靶点。结果 筛选出益肾达络饮活性成分115种预测靶点225个多发性硬化靶点8098个交集靶点199个,在生物学过程主要集中在炎症反应、氧化应激反应等,与IL-17信号通路、TNF通路关系密切,分子对接结果表明核心活性成分与核心靶点之间具有较强的结合活性,益肾达络饮对LPS诱导的星形胶质细胞炎性损伤具有明显保护作用,能够降低TNF-α、IL-1β表达(P<0.01)。结论 益肾达络饮主要通过抗炎、调节免疫应答促进轴突再生和髓鞘形成而发挥作用,益肾达络饮能够有效改善多发性硬化的相关指标。Objective: The mechanism of Yishen Daluo Decoction(YSDLD) in the treatment of multiple sclerosis(MS) was studied by network pharmacology method. The obtained target pathway was verified further. Methods: The active components, targets of YSDLD were obtained from TCMSP database and MS targets were obtained from GeneCards, OMIM, PharmGkb, TTD, and Drugbank databases. The intersection targets of YSDLD and MS were potential therapeutic targets. The active ingredient-target gene network and PPI network, GO, KEGG enrichment analysis results were obtained by cytoscape3.8.0, STRING, CytoNCA, R software. On this basis, molecular docking verification and in vitro experimental verification were carried out. Primary astrocytes of suckling rats were extracted and LPS was used to create the central inflammatory environment model of MS. The cell survival rate was detected by CCK-8. The TNF-α and IL-1β were detected by ELISA. Results: A total of 115 active components of YSDLD were obtained, corresponding to 225 targets. 8098 genes of MS and 199 genes of drug-disease intersection were obtained. In the biological process, inflammatory response and oxidative stress response were mainly concentrated, which were closely related to the interleukin-17(IL-17) signaling pathway and the TNF pathway. The molecular docking results showed that the core active components and core targets had strong binding activity. LPS-induced astrocyte inflammatory injury was significantly protected by YSDLD, which could reduce the expression of TNF-α and IL-1β(P<0.01). Conclusions: MS could be treated with YSDLD, which could effectively improve relevant indicators of MS by anti-inflammatory, regulating immune response and promoting axonal regeneration and myelination.

关 键 词：益肾达络饮 多发性硬化 作用机制 网络药理学 分子对接 

分 类 号：R593.25[医药卫生—内科学]