目的 采用GEO数据差异分析，探讨脑梗死疾病中可能存在的miRNA-mRNA互作模式，同时采用网络药理学方法，分析化痰通络汤联合丁苯酞在脑梗死疾病中的潜在机制，为中西医结合防治脑梗死疾病的深层机制进行探讨。方法 利用GEO、TargetScans、TCMSP、PubChem、Swiss Target Prediction数据库资源，采用Cytoscape 3.7.2、R语言软件，对脑梗死疾病中可能存在的miRNA-mRNA互作关系、化痰通络汤联合丁苯酞的治疗靶点、具体miRNA-mRNA互作模式在联合用药中的调控机制进行探讨。结果 脑梗死疾病中可能存在145个差异基因与32个miRNA构成520组miRNA-mRNA互作关系；化痰通络汤能单独调控14个靶点，如FGF2、STAT3、IL1B、JUN等，化痰通络汤与丁苯酞能联合调控4个靶点：HMOX1、TSPO、ICAM1、SELE；PPI、GO、KEGG富集及miRNA-mRNA-KEGG关联分析结果显示，联合用药能调节73组miRNA-mRNA互作关系，在6个细胞组分，通过5个分子功能，介导16条通路，在脑梗死的76个生命进程中发挥作用。结论 脑梗死疾病中可能存在520组miRNA-mRNA互作关系，其中化痰通络汤联合丁苯酞的能调控其中73组miRNAmRNA互作关系，以多组分、多功能、多途径的形式，介导TNF、p53、NF-κB、HIF-1等信号通路，在脑梗死疾病中发挥作用。

Objective To explore the possible interaction mode of miRNA-mRNA in cerebral infarction disease by using GEO data difference analysis, and to analyze the potential mechanism of Huatan Tongluo Decoction combined with butylphthalide in cerebral infarction disease by means of network pharmacology, so as to explore the deep mechanism of integrated traditional Chinese and western medicine in the prevention and treatment of cerebral infarction disease. Methods Using the database resources of GEO, TargetScans, TCMSP, PubChem and SwissTargetPrediction, and using Cytoscape3.7.2 and R language software, the possible miRNA-mRNA interaction relationship in cerebral infarction, the therapeutic target of Huatan Tongluo decoction combined with butylphthalide and the regulation mechanism of specific miRNA-mRNA interaction mode in the combined use of drugs were discussed. Results There may be 145 differential genes and 32 miRNA in cerebral infarction to form 520 miRNA-mRNA interaction relationship, Huatan Tongluo decoction can regulate 14 targets alone, such as FGF2, STAT3, IL1B, JUN, etc. Huatan Tongluo Decoction and butylphthalein can jointly regulate four targets, such as HMOX1, TSPO, ICAM1, SELE. The results of PPI, GO, KEGG enrichment and miRNA-mRNA-KEGG correlation analysis showed that the combination of drugs could regulate the interaction of miRNA-mRNA in 73 groups, and that six cellular components, 16 pathways, through five molecular functions, to play a role in 76 life processes of cerebral infarction. Conclusion There may be 520 groups of miRNA-mRNA interactions in cerebral infarction diseases. Huatan Tongluo Decoction combined with butylphthalide can regulate 73 groups of miRNA-mRNA interactions, mediate TNF, p53, NF-κB, HIF-1 and other signal pathways in the form of multi-components, multi-functions and multi-pathways, and play a role in cerebral infarction diseases.

R966

国家自然科学基金面上项目（81874463）；湖南省科技厅科技创新平台与人才计划（2017SK4005）；湖南省财政中医药项目名院工程院内优势病种项目（rsk-010-013/006-09）；常德市科技局项目（2018SK08）；湖南省中医药管理局资助项目（201824；202046；2020037）。