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姚尧尧,薛冰洁,武艺超,高颖.基于网络药理学和实验验证探讨补气通络颗粒治疗脑梗死的作用机制[J].湖南中医药大学学报英文版,2023,43(4):687-693.[Click to copy
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| 基于网络药理学和实验验证探讨补气通络颗粒治疗脑梗死的作用机制 |
| 姚尧尧,薛冰洁,武艺超,高颖 |
| (北京中医药大学, 北京 100029;北京中医药大学东直门医院, 北京 100700;北京中医药大学东直门医院, 北京 100700;国家中医药管理局脑病中医证治重点研究室, 北京 100700) |
| 摘要: |
| 目的 本研究采用网络药理学与实验验证探讨补气通络颗粒（以下简称“BQTL”）治疗脑梗死的潜在靶点、作用机制及物质基础。方法 通过TCMSP数据库及文献检索获得BQTL活性成分及靶点；利用GeneCards和OMIM数据库获取脑梗死的疾病靶点，将疾病靶点与BQTL成分靶点取交集得到潜在靶点，使用Cytoscape 3.9.0构建“药物-活性成分-潜在靶点”网络；通过STRING 11.0数据库构建蛋白质-蛋白质相互作用网络；利用Metascape平台对潜在靶点进行富集分析。根据网络药理学结果进行实验验证，组别设置为正常组、模型组、BQTL低剂量组、BQTL中剂量组、BQTL高剂量组，除正常组外，其余组制备短暂性大脑中动脉闭塞（transient middle cerebral artery occlusion, tMCAO）模型。正常组和模型组予以生理盐水灌胃，BQTL低、中、高剂量组分别以1.35、2.7、5.4 g/kg浓度的中药灌胃，每天灌胃1次，连续7 d。通过HE染色观察大鼠神经元形态及数目，使用ELISA试剂盒检测大鼠血浆中TNF-α和ICAM1的含量。结果 筛选后得到BQTL活性成分91个，主要包括柚皮素、芒柄花素、原儿茶酸等；治疗脑梗死的潜在靶点259个，主要包括ICAM1、TNF、EGFR、TP53、VCAM1、IL-6等；调控这些核心靶点的信号通路主要富集在PI3K-AKT、MAPK、HIF-1等多条信号通路中。动物实验结果显示，BQTL能够改善脑梗死后神经元死亡及丢失，同时能下调炎症因子TNF-α及ICAM1的表达。结论 BQTL通过多靶点、多途径抑制炎症反应和细胞凋亡，揭示了BQTL治疗脑梗死的潜在靶点、作用机制及物质基础，为临床应用提供参考。 |
| 关键词: 补气通络颗粒 脑梗死 网络药理学 实验验证 |
| DOI：10.3969/j.issn.1674-070X.2023.04.018 |
| Received:July 19, 2022 |
| 基金项目:中医药传承与创新“百千万”人才工程（岐黄工程）（国中医药人教发〔2018〕12号）。 |
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| Mechanisms of Buqi Tongluo Granule in treating cerebral infarction based on network pharmacology and experimental verification |
| YAO Yaoyao,XUE Bingjie,WU Yichao,GAO Ying |
| (Beijing University of Chinese Medicine, Beijing 100029, China;Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing 100700, China;Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing 100700, China;Key Laboratory of TCM Treatment of Encephalopathy, State Administration of Chinese Medicine, Beijing 100700, China) |
| Abstract: |
| Objective To investigate the potential targets, mechanism and material basis of Buqi Tongluo Granule (BQTL) in treating cerebral infarction by network pharmacology and experimental verification.Methods Active constituents and targets of BQTL were identified by TCMSP database and literature search. Disease targets of cerebral infarction were obtained by using GeneCards and OMIM databases, and the intersection of disease targets and BQTL constituent targets was used to verify the potential targets. Then, the "drug-active constituent-potential target" network was constructed by Cytoscape 3.9.0. The protein protein interaction network was established through STRING 11.0 database. The Metascape platform was used to enrich potential targets. Based on the network pharmacological results, the experimental verification was performed. Normal group, model group, low-, medium- and high-dose BQTL groups were set. Transient middle cerebral artery occlusion (tMCAO) model was prepared in all groups except normal group. Normal group and model group were given normal saline intragastrically, while low-, medium- and high-dose BQTL groups received 1.35, 2.7 and 5.4 g/kg Chinese medicine intragastrically, once a day, for consecutive 7 d. The morphology and number of rat neurons were observed by HE staining, and the content of TNF-α and ICAM1 in rat plasma were detected by ELISA kit.Results After screening, 91 active ingredients of BQTL were obtained, including naringenin, formononetin, protocatechuic acid, and others. There were 259 potential targets to treat cerebral infarction, including ICAM1, TNF, EGFR, TP53, VCAM1, IL-6, and others. The signaling pathways regulating these core targets were mainly concentrated in PI3K-AKT, MAPK, HIF-1 and other signaling pathways. Animal experiments showed that BQTL could reduce neuronal death and loss after cerebral infarction, and down-regulate the inflammatory cytokines, of TNF-α and ICAM1.Conclusion BQTL inhibits inflammation and apoptosis through multiple targets and multiple pathways. The study reveals the potential target, mechanisms of action and material basis of BQTL for cerebral infarction, providing reference for clinical application. |
| Key words: Buqi Tongluo Granule cerebral infarction network pharmacology experimental verification |
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