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
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摘要
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.
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.
引文
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[11] Umar A,Guerin V,Renard M,et al. Effects of armagnac extracts on human platelet function in vitro and on rat arteriovenous shunt thrombosis in vivo[J]. Thromb Res,2003,110(2/3):135.
[12]段文娟,赵伟,李月,等.瓜蒌不同部位对斑马鱼促血管生成及心脏保护作用[J].中成药,2017,39(6):1261.
[13]谭斌,刘思妤,王桂霞,等.瓜蒌皮提取物对大鼠血管内皮功能的影响[J].中南医学科学杂志,2015,43(5):506.
[14]杨征,宋淼,陈强,等.瓜蒌皮提取物对AngⅡ诱导血管平滑肌细胞增殖的影响[J].临床合理用药,2018,11(1A):44.
[15]杨征,郭晓华,宋淼,等.瓜蒌皮提取物对大鼠血栓形成的影响[J].中国实用医药,2018,13(5):197.
[16]赵启韬.瓜蒌皮注射液对缺血缺氧的内皮祖细胞保护作用[J].中成药,2015,37(2):247.
[17]文琳,谷彬,曹喻灵,等.瓜蒌皮总黄酮对LDL诱导的大鼠血管内皮损伤的保护作用[J].湘南学院学报:医学版,2016,18(2):13.
[18]李莹,王磊沙,刘建勋,等.脑梗死气虚血瘀证大鼠模型表征及病理生理变化研究[J].中国中药杂志,2018,43(4):786.
[19]史雅红,任建勋,刘建勋,等.睡眠剥夺诱导的大鼠血瘀证对血小板活化影响的研究[J].中国中药杂志,2018,43(16):3341.
[2]邹纯才,吕文雅,周雨婷,等.瓜蒌薤白配伍抗凝血作用的研究[J].通化师范学院学报,2018,39(12):15.
[3]邹纯才,洪国君,鄢海燕.不同数据标准化方法对瓜蒌滴丸抗凝血作用谱效关系的影响[J].中国中药杂志,2018,43(9):1864.
[4]刘岱琳,曲戈霞,王乃利,等.瓜蒌的抗血小板聚集活性成分研究[J].中草药,2004,35(12):1334.
[5] Takano F,Yoshizaki F,Suzuki K,el al. Anti-ulcer effects of Trichosanthes fruits[J].Chem Pharm Bull,1990,38(5):1313.
[6]王辉俊,柯樱,叶冠.活性导向分离瓜蒌皮中具有抗血管紧张素转化酶作用的成分[J].中国中药杂志,2017,42(16):3131.
[7]刘颁,石振东.瓜蒌皮注射液联合阿司匹林治疗高龄不稳定型心绞痛的临床效果及对血小板聚集率的影响[J].中国疗养医学,2016,25(2):188.
[8]王莉丽,邹纯才,鄢海燕,等.复方瓜蒌-阿司匹林微丸胶囊的制备及其释药性评价[J].国际药学研究杂志,2018,45(7):531.
[9]鄢海燕,邹纯才,王莉丽,等.一种复方瓜蒌-阿司匹林胃肠溶微丸胶囊及其制备方法和应用:中国,201711251933. 8[P].2017-12-01.
[10] Umar A,Boisseau M,Yusup A,et al. Interactions between aspirin and COX-2 inhibitors or NSAIDs in a rat thrombosis model[J]. Fund Clin Pharmacol,2004,18(5):559.
[11] Umar A,Guerin V,Renard M,et al. Effects of armagnac extracts on human platelet function in vitro and on rat arteriovenous shunt thrombosis in vivo[J]. Thromb Res,2003,110(2/3):135.
[12]段文娟,赵伟,李月,等.瓜蒌不同部位对斑马鱼促血管生成及心脏保护作用[J].中成药,2017,39(6):1261.
[13]谭斌,刘思妤,王桂霞,等.瓜蒌皮提取物对大鼠血管内皮功能的影响[J].中南医学科学杂志,2015,43(5):506.
[14]杨征,宋淼,陈强,等.瓜蒌皮提取物对AngⅡ诱导血管平滑肌细胞增殖的影响[J].临床合理用药,2018,11(1A):44.
[15]杨征,郭晓华,宋淼,等.瓜蒌皮提取物对大鼠血栓形成的影响[J].中国实用医药,2018,13(5):197.
[16]赵启韬.瓜蒌皮注射液对缺血缺氧的内皮祖细胞保护作用[J].中成药,2015,37(2):247.
[17]文琳,谷彬,曹喻灵,等.瓜蒌皮总黄酮对LDL诱导的大鼠血管内皮损伤的保护作用[J].湘南学院学报:医学版,2016,18(2):13.
[18]李莹,王磊沙,刘建勋,等.脑梗死气虚血瘀证大鼠模型表征及病理生理变化研究[J].中国中药杂志,2018,43(4):786.
[19]史雅红,任建勋,刘建勋,等.睡眠剥夺诱导的大鼠血瘀证对血小板活化影响的研究[J].中国中药杂志,2018,43(16):3341.
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