| 引用本文: |
朱秋燕,曾鑫冰,杨筱倩,谢若曦,李笑,黄小平,邓常清.益气活血开窍组分中药对脑缺血后白质保护的网络药理学研究及药效学验证[J].湖南中医药大学学报,2022,42(6):941-949[点击复制] |
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| 益气活血开窍组分中药对脑缺血后白质保护的网络药理学研究及药效学验证 |
| 朱秋燕,曾鑫冰,杨筱倩,谢若曦,李笑,黄小平,邓常清 |
| (湖南中医药大学血管生物学实验室, 湖南 长沙 410208;湖南中医药大学中西医结合心脑疾病防治湖南省重点实验室, 湖南 长沙 410208;湖南中医药大学医学院, 湖南 长沙 410208) |
| 摘要: |
| 目的 采用网络药理学方法，以髓鞘再生的主要功能细胞少突胶质前体细胞（oligodendrocyte precursor cells,OPCs）为靶点，预测益气活血开窍组分中药有效成分对脑缺血后白质损伤的促修复作用。方法 从TCMSP、PubChem、SwissTargetPrediction数据库中预测组分中药主要有效成分促进脑卒中后OPCs修复脑白质的作用靶点；整合GEO、GeneCards和CTD数据库中获得的脑卒中疾病靶基因，通过STRING绘制“中药组分-疾病”靶点PPI网络图；并进行GO及KEGG富集分析。同时，采用大鼠脑缺血再灌注模型，从神经功能和形态学评价益气活血开窍组分中药对脑缺血再灌注后脑白质损伤的促修复作用。结果 网络药理学共获取33个疾病-药物共同潜在靶点。PPI网络及拓扑分析结果显示VEGFA、PTGS2、NTRK1、ESR2和MET等可能为核心作用靶点，富集分析主要涉及钙离子、PI3K-Akt、VEGF、Rap1、Ras、EGFR酪氨酸激酶抑制剂抗性和MAPK信号通路，KEGG富集分析GEO数据集差异基因结果显示，卒中5 d和15 d均涉及PI3K-Akt信号通路。药理学实验结果显示，益气活血开窍组分中药可改善脑缺血再灌注后大鼠神经功能障碍，减轻脑白质损伤和大鼠胼胝体、纹状体髓鞘脱失。结论 益气活血开窍组分中药可改善脑缺血再灌注后白质损伤，机制可能与各有效成分通过多靶点、多途径促进髓鞘再生和白质修复有关。 |
| 关键词: 网络药理学 益气活血开窍组分中药 脑缺血再灌注 髓鞘再生 |
| DOI：10.3969/j.issn.1674－070X.２０22.06.012 |
| 投稿时间：2021-12-07 |
| 基金项目:湖南省教育厅重点项目(19A381);长沙市自然科学基金项目(kq2014084);2022年湖南省中医药管理局重点项目(E2022001);2022年湖南省国内一流培育学科中西医结合学科项目(2021ZXYJH06);2021年湖南中医药大学校级科研基金项目(2021XJJJ027);2020年湖南省大学生创新创业训练计划项目(2598);2021年国家级大学生创新创业训练计划项目(202110541053);湖南中医药大学"十三五"一级学科基础医学建设项目(06);湖南省研究生优秀教学团队(基础医学研究生教学团队)项目([2019]370-118);2022年湖南省自然科学基金项目(631)。 |
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| Network pharmacology reseach and pharmacodynamic validation of the ingredient Chinese medicine with Qi-benefiting, blood-activating and resuscitation on white matter protection after cerebral ischemia |
| ZHU Qiuyan,ZENG Xinbing,YANG Xiaoqian,XIE Ruoxi,LI Xiao,HUANG Xiaoping,DENG Changqing |
| (Laboratory of Vascular Biology, Hunan University of Chinese Medicine, Changsha, Hunan 410208, China;Hunan Key Laboratory of Cerebrovascular Disease Prevention and Treatment of Integrated Traditional Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha, Hunan 410208, China;Medical College of Hunan University of Chinese Medicine, Changsha, Hunan 410208, China) |
| Abstract: |
| Objective Through network pharmacology, to predict the promoting and repairing effect of effective components of the ingredient Chinese medicine with Qi-benefiting, blood-activating and resuscitation on white matter injury after cerebral ischemia with oligodendrocyte precursor cells (OPCs), the main functional cells of myelin regeneration. Methods TCMSP, PubChem and SwissTargetPrediction databases were used to predict the targets of the effective components of ingredient Chinese medicine in promoting white matter repair of OPCs after stroke; GEO, GeneCards and CTD databases were used to search the stroke targets; PPI network diagram of "ingredient Chinese medicine-disease" targets was drew through STRING, and preformed for GO and KEGG enrichment analysis. Meanwhile, using the rat cerebral ischemia-reperfusion model, the promoting and repairing effect of effective components of the ingredient Chinese medicine with Qi-benefiting, blood-activating and resuscitation on white matter injury after cerebral ischemia was evaluated from neurological function and morphology. Results A total of 33 drug-disease common potential targets were identified in network pharmacology. PPI network and topology analysis revealed that VEGFA, PTGS2, NTRK, ESR2 and MET, etc. may be important targets, enrichment analysis mainly involved Calcium, PI3K-Akt, VEGF, Rap1, Ras, EGFR tyrosine kinase inhibitor resistance and MAPK signaling pathways. KEGG enrichment analysis of differential genes in GEO data sets showed, PI3K-Akt signialing pathway was involved in both 5 and 15 days of stroke. Pharmacological experiments showed that the ingredient Chinese medicine with Qi-benefiting, blood-activating and resuscitation can improve neurological function and mitigate white matter injury after cerebral ischemia-reperfusion, reduce white matter injury and demyelination of corpus callosum and striatum in rats. Conclusion The ingredient Chinese medicine with Qi-benefiting, blood-activating and resuscitation can effectively improve white matter injury after cerebral ischemia-reperfusion and the effect may be closely related to the multi-target and multi-pathway promotion of myelin regeneration and white matter repair by each active ingredient. |
| Key words: network pharmacology ingredient Chinese medicine with Qi-benefiting, blood-activating and resuscitation cerebral ischemia-reperfusion remyelination |
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