[关键词]
[摘要]
目的 基于人用经验、网络药理学和分子对接探讨有效单味药鸡血藤治疗重症肌无力的作用机制。 方法 通过中药系统药理学数据库与分析平台(TCMSP)筛选鸡血藤活性成分及其靶点,结合 GeneCards 和 OMIM 数据库获取重症肌无力相关靶点。利用 Uniprot 统一靶点命名后,取两者交集靶点进行后续分析。利用 Cytoscape 3.7.1 软件构建药物组分-靶点网络,基于 STRING 平台创建蛋白互作网络。运用 DAVID 开展 GO 注 释和 KEGG 通路富集分析。用 AutoDock Vina 完成活性成分与核心靶点的分子对接验证。 结果 鸡血藤中共 筛选出 23 种活性化合物(如木犀草素等)及 128 个作用靶点;重症肌无力对应疾病靶点有 1 115 个,鸡血藤和 重症肌无力共有 31 个交集靶点,筛选出核心靶点 13 个,其中节点应力(Node Stress)值最高为乙酰胆碱酯酶 (AChE);富集分析显示,鸡血藤或可通过调控 154 条信号通路(如内分泌抵抗、AGE-RAGE 信号通路等)来介 入重症肌无力发病过程。以上核心靶点和通路参与重症肌无力相关病理机制,包括 AChE 活性异常、神经肌肉 接头损坏、突触可塑性改变、巨噬细胞对乙酰胆碱受体(AChR)的吞噬作用、自身反应性淋巴细胞凋亡受阻、 免疫耐受缺陷以及内分泌抵抗等。分子对接结果提示木犀草素与 AChE 结合展现出最高亲和力,其次是刺芒柄 花素、毛蕊异黄酮与 AChE 的结合。结论 鸡血藤治疗重症肌无力可能与调节 AChE 活性、调整自噬过程、促 进自身反应性淋巴细胞凋亡及减少内分泌抵抗等有关。鸡血藤所含的木犀草素可降低抗 AChR 抗体,抑制 AChE 活性,减少巨噬细胞对 AChR 的吞噬,治疗重症肌无力伴记忆减退者,有较高开发价值。但鸡血藤治疗 重症肌无力伴胸腺瘤存在争议,值得进一步讨论。
[Key word]
[Abstract]
Objective To investigate the mechanism of the effective single herb Spatholobi Caulis in treating myasthenia gravis (MG) based on human experience, network pharmacology, and molecular docking. Methods Active components of Spatholobi Caulis and their targets were screened using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). MG-related targets were obtained from GeneCards and OMIM databases. After unifying target names with Uniprot,intersection targets were identified for subsequent analysis. A drug component-target network was constructed using Cytoscape 3.7.1,and a protein-protein interaction (PPI) network was established based on the STRING platform. GO annotation and KEGG pathway enrichment analyses were performed using DAVID. Molecular docking verification of active components with core targets was completed using AutoDock Vina. Results A total of 23 active compounds (such as luteolin) and 128 action targets were screened from Spatholobi Caulis. There were 1 115 disease targets corresponding to MG,with 31 shared targets between Spatholobi Caulis and MG. Thirteen core targets were identified,among which acetylcholinesterase (AChE) showed the highest Node Stress value. Enrichment analysis revealed that Spatholobi Caulis might intervene in the pathogenesis of MG by regulating 154 signaling pathways (such as endocrine resistance and AGE-RAGE signaling pathway). These core targets and pathways participate in MG-related pathological mechanisms, including abnormal AChE activity, neuromuscular junction damage,altered synaptic plasticity,macrophage phagocytosis of acetylcholine receptor (AChR),impaired apoptosis of autoreactive lymphocytes,immune tolerance defects,and endocrine resistance. Molecular docking results indicated that luteolin exhibited the highest binding affinity with AChE,followed by formononetin and calycosin binding to AChE. Conclusion Spatholobi Caulis may treat MG by regulating AChE activity,modulating autophagy processes, promoting apoptosis of autoreactive lymphocytes,and reducing endocrine resistance. Luteolin contained in Spatholobi Caulis can reduce anti-AChR antibodies,inhibit AChE activity,and decrease macrophage phagocytosis of AChR, showing high development value for treating MG accompanied by memory impairment. However,the use of Spatholobi Caulis for MG with thymoma remains controversial and warrants further discussion.
[中图分类号]
R285.5
[基金项目]
广东省医学科学技术研究基金项目(B2021155);第七批“全国老中医药专家学术经验继承工作”项目(国中医药人教函[2022]76号); 第五批全国中医临床优秀人才研修项目(国中医药人教函[2022]239号);刘小斌省名中医传承工作室建设项目(粤中医办函 〔2023〕 108 号); 广州中医药大学揭榜挂帅项目(广中医校办[2024]163号)。