基于药物代谢组学方法研究益气活血中药有效部位配伍增强阿司匹林抗血小板作用的机理

Aspirin resistance (AR) is one of the most serious factors leading the patient with cardiovascular and cerebrovascular diseases to thrombotic events reoccurring. The prevalent treatment of AR is to increase its amount or to use with other anti-platelet medicines, which caused serious bleeding and gastric mucosal injury for long time use. Panax notoginseng saponin (PNS) and total saponin from stems and leaves of Panax quinquefolium (PQS) are the commonly used China Patent drugs for coronary heart disease in clinical, which are found to have the potential to enhance the anti-platelet effect of aspirin by simultaneously used with aspirin. But the underlying mechanism is poorly understood. . To uncover the possible mechanism, the pharmacometabolomics methods basing on LC-MS or GC-MS analysis will be applied to study on the differentiated metabolomic in the AMI rats’ plasma of simultaneous use of aspirin, PQS and PNS to verify whether the purine pathway plays important role in the anti-platelet effect of compatibility use of aspirin, PQS and PNS as it does in anti-AR. And the uncovered differentiated metabolomic will be screened by their metabolic pathways and by associated function analysis to elucidate the underlying mechanism of the enhanced-antiplatelet effect of the compatibility use of aspirin, PQS and PNS. The results will be helpful for the comprehensive understand of the compatibility use of aspirin, PQS and PNS to enhance the antiplatelet effect of aspirin in clinical trials..

阿司匹林抵抗（AR）是心脑血管病患者再发血栓事件的重要因素，目前应对措施是加大阿司匹林用量或与其他抗血小板药物联用，但出现了出血、胃黏膜损伤等问题。三七总皂苷（PNS）和西洋参茎叶总皂苷（PQS）是常用治疗冠心病的中药有效部位制剂，临床观察证明和阿司匹林联用，可缓解阿司匹林所致的胃黏膜损伤，提高阿司匹林的抗血小板作用，但缺少相互作用的机理研究。. 本课题拟采用基于LC-MS和GC-MS的药物代谢物组学方法，以与AR显著相关的嘌呤代谢途径为切入点，研究阿司匹林+PQS+PNS配伍用药对急性心肌梗死（AMI）大鼠血浆嘌呤途径代谢物组的影响，探讨配伍用药增强阿司匹林抗血小板聚集作用是否与AR相关；同时系统研究各组AMI大鼠血浆代谢物组轮廓差异，筛选配伍用药的差异代谢物组，通过代谢通路关联分析，阐释PQS+PNS配伍增强阿司匹林抗血小板聚集作用的机制，为临床合理用药提供科学依据。