目的 采用GEO數(shù)據(jù)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(shí)采用網(wǎng)絡(luò)藥理學(xué)方法，分析化痰通絡(luò)湯聯(lián)合丁苯酞在腦梗死疾病中的潛在機(jī)制，為中西醫(yī)結(jié)合防治腦梗死疾病的深層機(jī)制進(jìn)行探討。方法 利用GEO、TargetScans、TCMSP、PubChem、Swiss Target Prediction數(shù)據(jù)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(guān)系、化痰通絡(luò)湯聯(lián)合丁苯酞的治療靶點(diǎn)、具體miRNA-mRNA互作模式在聯(lián)合用藥中的調(diào)控機(jī)制進(jìn)行探討。結(jié)果 腦梗死疾病中可能存在145個(gè)差異基因與32個(gè)miRNA構(gòu)成520組miRNA-mRNA互作關(guān)系；化痰通絡(luò)湯能單獨(dú)調(diào)控14個(gè)靶點(diǎn)，如FGF2、STAT3、IL1B、JUN等，化痰通絡(luò)湯與丁苯酞能聯(lián)合調(diào)控4個(gè)靶點(diǎn)：HMOX1、TSPO、ICAM1、SELE；PPI、GO、KEGG富集及miRNA-mRNA-KEGG關(guān)聯(lián)分析結(jié)果顯示，聯(lián)合用藥能調(diào)節(jié)73組miRNA-mRNA互作關(guān)系，在6個(gè)細(xì)胞組分，通過5個(gè)分子功能，介導(dǎo)16條通路，在腦梗死的76個(gè)生命進(jìn)程中發(fā)揮作用。結(jié)論 腦梗死疾病中可能存在520組miRNA-mRNA互作關(guān)系，其中化痰通絡(luò)湯聯(lián)合丁苯酞的能調(diào)控其中73組miRNAmRNA互作關(guān)系，以多組分、多功能、多途徑的形式，介導(dǎo)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(xué)基金面上項(xiàng)目（81874463）；湖南省科技廳科技創(chuàng)新平臺與人才計(jì)劃（2017SK4005）；湖南省財(cái)政中醫(yī)藥項(xiàng)目名院工程院內(nèi)優(yōu)勢病種項(xiàng)目（rsk-010-013/006-09）；常德市科技局項(xiàng)目（2018SK08）；湖南省中醫(yī)藥管理局資助項(xiàng)目（201824；202046；2020037）。