香草酸抗血小板聚集作用的体内外研究  

Antiplatelet Aggregation Effect of Vanillic Acid In Vitro and In Vivo

作　　者：孔令雷 王海港 刘成娣 张森 刘楠楠 马国栋 杜冠华 KONG Linglei;WANG Haigang;LIU Chengdi;ZHANG Sen;LIU Nannan;MA Guodong;DU Guanhua(Beijing Key Laboratory of Drug Target and Screening Research,Institute of Materia Medica,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100050,China;Guangdong Pharmaceutical University,Guangzhou Guangdong 510006,China)

机构地区：[1]中国医学科学院,北京协和医学院药物研究所,药物靶点研究与新药筛选北京市重点实验室,北京100050 [2]广东药科大学,广东广州510006

出　　处：《中国药物警戒》2020年第6期342-347,共6页Chinese Journal of Pharmacovigilance

基　　金：“重大新药创制”科技重大专项(2018ZX09711001-009-009);北京市自然科学基金面上项目(7182113);中国医学科学院医学与健康科技创新工程(2016-I2M-3-007)。

摘　　要：目的香草酸是一种酚酸类化合物,具有抗氧化、抗炎等药理作用,其抗血栓作用尚未有报道。本实验室前期通过筛选发现香草酸具有良好的抗血小板聚集作用,因此本研究通过体内外实验对香草酸抗血小板聚集的作用进行系统评价。方法采用花生四烯酸(arachidonic acid,AA)、二磷酸腺苷(adenosine diphosphate,ADP)、凝血酶(thrombin,THR)诱导体内外血小板聚集模型,结合凝血四项检测评价香草酸抗血小板聚集及抗血栓的作用。结果体外实验中,香草酸对ADP和AA诱导的血小板聚集具有显著抑制作用,并剂量依赖性抑制ADP诱导的血小板聚集;体内试验中,香草酸(10、30和100 mg/kg)能够剂量依赖性抑制ADP和AA诱导的血小板聚集;同时,香草酸(100 mg/kg)能显著降低纤维蛋白原、增加凝血酶原时间,对活化部分凝血活酶时间和血浆凝血酶时间无明显影响。结论本研究首次发现香草酸对ADP和AA诱导的血小板聚集具有抑制作用,为研发具有自主知识产权的抗血小板聚集药物提供了实验依据。Objective To evaluate systematically in vivo and in vitro the anti-platelet aggregation effect of vanillic acid(VAA),which is a phenolic compound with antioxidant and anti-inflammatory properties.Methods A platelet aggregation model induced by arachidonic acid(AA),adenosine diphosphate(ADP)and thrombin(THR)was used to evaluate the antithrombotic effect of VAA in vitro and in vivo.Results In vitro,VAA significantly inhibited platelet aggregation induced by ADP and AA.And it could inhibit platelet aggregation induced by ADP in a dose-dependent manner.The results of in vivo experiments also showed that VAA(10,30 and 100 mg/kg)decreased platelet aggregation induced by ADP and AA in a dose-dependent manner.In addition,VAA(100 mg/kg)could significantly reduce fibrinogen and increase prothrombin time,but had little effect on activated partial thromboplastin time and thrombin time.Conclusion VAA could inhibit platelet aggregation induced by ADP and AA,which provides reference for the development of new antiplatelet drugs.

关 键 词：香草酸 血栓性疾病 血小板聚集 

分 类 号：R965[医药卫生—药理学]