龚翠兰 周德生 杨仁义 傅馨莹

摘要 目的：采用GEO芯片數据及网络药理学方法，分析脑梗死疾病基因，并对化痰通络汤治疗脑梗死风痰阻络证的作用机制进行探讨，为脑梗死的中医药防治提供理论依据。方法：采用多学科交叉方法对化痰通络汤治疗脑梗死风痰阻络证进行研究，整合GEO、GeneCards、TCMSP、PubChem、Swiss Target Prediction、String、WebGestalt数据库资源，利用Cytoscape、R语言软件，对脑梗死差异基因、疾病靶点、化痰通络汤的中药有效成分、中药靶点进行筛选，从蛋白质-蛋白质相互作用（PPI）共表达网络、GO及KEGG富集分析角度，探讨化痰通络汤治疗脑梗死风痰阻络证的所用机制。结果：获取3 110个脑梗死疾病靶点，其中203个差异基因，198个在脑梗死疾病中表达上调，5个在脑梗死疾病中表达下调，可作为诊断及治疗的潜在靶点。PPI网络及Degree、Betweenness、Closeness算法拓扑分析结果显示，PI3KCA、MAPK1、EGFR等48个靶点相互作用最强，可作为后续基础研究验证方向。GO、KEGG富集分析结果显示，BP共富集354个生物进程，CC共富集16个细胞组分，MF共富集29个分子功能，KEGG共富集137个信号通路，结合FDR、ratio与P值结果对富集分析结果进行权重分析，进一步聚焦其富集结果。结论：化痰通络汤可针对性上调GFAP、CD14、STAT3、H19、CXCL16等，下调NAT8F3、OLR59、GPR88等，以多组分、多功能、多途径的形式介导鞘脂信号通路、VEGF通路、HIF-1通路等多通路在脑梗死风痰阻络证中发挥作用。

关键词 基因表达综合;差异基因;化痰通络汤;脑梗死;网络药理学;风痰阻络证;KEGG富集分析;靶点

Abstract Objective：To analyze the disease genes of cerebral infarction by GEO chip data and network pharmacology methods，and to explore the mechanism of Huatan Tongluo Decoction in the treatment of cerebral infarction with the syndrome of wind-phlegm obstructing collaterals，so as to provide theoretical basis for the prevention and treatment of cerebral infarction with traditional Chinese medicine（TCM）.Methods：Interdisciplinary methods were used to study the treatment of Huatan Tongluo Decoction for syndrome of wind-phlegm obstructing collaterals of cerebral infarction.The database resources of GEO，GeneCards，TCMSP，PubChem，Swiss Target Prediction，String and WebGestalt were integrated，and the differential genes of cerebral infarction，disease targets，effective components and targets of Huatan Tongluo Decoction were screened by Cytoscape and R language software.From the point of view of PPI co-expression network，GO and KEGG enrichment analysis，the mechanism of Huatan Tongluo Decoction in treating cerebral infarction with syndrome of wind-phlegm obstructing collaterals was explored tentatively.Results：A total of 3 110 targets of for cerebral infarction diseases were obtained， of which there were 203 differential genes. There were 198 up-regulated in cerebral infarction diseases， and there were 5 down-regulated in cerebral infarction diseases， which can be used as potential targets for diagnosis and treatment.The topology analysis results of PPI network，Degree，Betweenness，and Closeness algorithms showed that 48 targets such as PI3KCA，MAPK1 and EGFR interacted most strongly，which can be used as the direction of follow-up basic research.The results of GO and KEGG enrichment analysis showed that BP enriched 354 life processes，CC enriched 16 cell components，MF enriched 29 Molecular functions，and KEGG enriched 137 signal pathways.Combined with the results of FDR，ratio and P value，the weight analysis results were analyzed to further focus on the enrichment results.Conclusion：Huatan Tongluo Decoction could up-regulate/down-regulate target genes（up-regulated GFAP，CD14，STAT3，H19，CXCL16，etc. and down-regulate NAT8F3，OLR59，GPR88，etc.）in the form of multi-component，multi-function and multi-pathway，mediate sphingolipid signal pathway，VEGF pathway，HIF-1 pathway and other pathways were playing a roles in the syndrome of wind-phlegm obstructing collaterals in cerebral infarction.

Keywords Gene Expression Omnibus; Differential gene; Huatan Tongluo Decoction; Cerebral infarction; Network pharmacology; Syndrome of wind phlegm obstructing collaterals; KEGG enrichment analysis; Target

中图分类号：R255.2;R743.3文献标识码：Adoi：10.3969/j.issn.1673-7202.2021.09.010

脑梗死属中医“缺血中风”范畴，是临床常见病、多发病，具有高致残率、致死率的特点，严重危害人类健康，因此脑梗死的中医药防治具有重要意义[1]。……