基于网络药理学分析瓜蒌阿司匹林配伍抗血小板聚集和抗血栓的作用机制研究

Anti-platelet aggregation and anti-thrombotic mechanism of Trichosanthis Fructus combined with aspirin based on network pharmacology

基于网络药理学预测及大鼠动静脉旁路模型验证方法,对瓜蒌阿司匹林配伍抗血小板聚集和抗血栓作用机制进行探讨。运用TCMSP,DRAR-CPI,Uniprot,DAVID数据库进行蛋白靶点预测及生物途径和信号通路分析,预测瓜蒌阿司匹林配伍的作用机制。考察瓜蒌微丸、阿司匹林微丸及瓜蒌微丸阿司匹林微丸配伍预处理对大鼠血栓模型血栓素B2(thromboxane B2,TXB2)、6-酮-前列腺素F1α(6-keto prostaglandin F1α,6-keto-PGF1α)、环磷酸腺苷(cyclic adenosine monophosphate,c AMP)的影响。通过网络药理学研究发现,阿司匹林及瓜蒌中hydroxygenkwanin,quercetin,adenosine等12个成分通过SRC,RAC1,MAPK14,MAPK1,AKT1等9个共同的蛋白靶点、VEGF signaling pathway等14条共同信号通路协同发挥抗血小板聚集和抗血栓作用。瓜蒌微丸阿司匹林微丸配伍预处理可通过激活大鼠血管内皮生长因子(vascular endothslia growth factor,VEGF)信号通路,抑制血小板聚集及改善血管内皮功能发挥抗血小板聚集和抗血栓作用,验证了网络药理学结果,阐释了瓜蒌微丸阿司匹林微丸配伍抗血小板聚集和抗血栓的作用机制。

To explore the anti-platelet aggregation and anti-thrombotic mechanisms of Trichosanthis Fructus combined with aspirin based on network pharmacology and the validation of arteriovenous by pass model in rats.The databases of Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),Drug Repositioning and Adverse Drug Reaction Chemical-Protein Interactome(DRAR-CPI),Universal Protein Resource(Uniprot)and the Database for Annotation,Visualization,and Integrated Discovery(DAVID)were used to predict protein targets and analyze biological pathway and signal pathway in the combination of Trichosanthis Fructus with aspirin.The effects of pretreatment with Trichosanthis Fructus pellets,aspirin pellets and their combination on thromboxane B2(TXB2),6-keto prostaglandin F1α(6-keto-PGF1α)and cyclic adenosine monophosphate(c AMP)in rat thrombotic model were studied.Through the study of network pharmacology,12 components of aspirin and Trichosanthis Fructus,including hydroxygenkwanin,quercetin and adenosine,were found to show the anti-platelet aggregation and anti-thrombosis mechanisms through9 common protein targets,such as SRC,RAC1,MAPK14,MAPK1,AKT1,and 14 common signaling pathways,such as VEGF signaling pathway.After the intervention with Trichosanthis Fructus pellets combined with aspirin pellets,the vascular endothslia growth factor(VEGF)signaling pathway can be activated to inhibit platelet aggregation and improve vascular endothelial function,and show the anti-platelet aggregation and anti-thrombosis mechanisms,which verify the results of the network pharmacology,and explain the anti-platelet aggregation and anti-thrombotic mechanisms of the combination of Trichosanthis Fructus pellets with aspirin pellets.