目的 采用GEO數據差異分析，探討腦梗死疾病中可能存在的miRNA-mRNA互作模式，同時采用網絡藥理學方法，分析化痰通絡湯聯(lián)合丁苯酞在腦梗死疾病中的潛在機制，為中西醫(yī)結合防治腦梗死疾病的深層機制進行探討。方法 利用GEO、TargetScans、TCMSP、PubChem、Swiss Target Prediction數據庫資源，采用Cytoscape 3.7.2、R語言軟件，對腦梗死疾病中可能存在的miRNA-mRNA互作關系、化痰通絡湯聯(lián)合丁苯酞的治療靶點、具體miRNA-mRNA互作模式在聯(lián)合用藥中的調控機制進行探討。結果 腦梗死疾病中可能存在145個差異基因與32個miRNA構成520組miRNA-mRNA互作關系；化痰通絡湯能單獨調控14個靶點，如FGF2、STAT3、IL1B、JUN等，化痰通絡湯與丁苯酞能聯(lián)合調控4個靶點：HMOX1、TSPO、ICAM1、SELE；PPI、GO、KEGG富集及miRNA-mRNA-KEGG關聯(lián)分析結果顯示，聯(lián)合用藥能調節(jié)73組miRNA-mRNA互作關系，在6個細胞組分，通過5個分子功能，介導16條通路，在腦梗死的76個生命進程中發(fā)揮作用。結論 腦梗死疾病中可能存在520組miRNA-mRNA互作關系，其中化痰通絡湯聯(lián)合丁苯酞的能調控其中73組miRNAmRNA互作關系，以多組分、多功能、多途徑的形式，介導TNF、p53、NF-κB、HIF-1等信號通路，在腦梗死疾病中發(fā)揮作用。

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

國家自然科學基金面上項目（81874463）；湖南省科技廳科技創(chuàng)新平臺與人才計劃（2017SK4005）；湖南省財政中醫(yī)藥項目名院工程院內優(yōu)勢病種項目（rsk-010-013/006-09）；常德市科技局項目（2018SK08）；湖南省中醫(yī)藥管理局資助項目（201824；202046；2020037）。