活血化瘀中药通过血小板P2Y12受体后信号通路调控氯吡格雷低反应的机制研究

氯吡格雷是临床主要的抗血小板药物，其低反应是心血管事件发生的独立危险因素。P2Y12受体后信号通路不仅是影响氯吡格雷反应性的重要通路，也是干预氯吡格雷低反应的可能作用靶点。活血化瘀中药川芎、赤芍有效部位皆有抗血小板作用，但其可否通过调控P2Y12受体后信号通路发挥改善氯吡格雷低反应作用，尚未见报道。本研究通过体外人血小板实验（氯吡格雷低反应人群、健康人），研究活血化瘀中药川芎、赤芍有效部位对氯吡格雷低反应的调控机制；通过apoE基因敲除小鼠动脉粥样硬化模型、冠脉微血栓大鼠模型，从斑块稳定性和微血栓形成两个层面，研究活血化瘀中药川芎、赤芍有效部位对P2Y12受体后信号通路的调控作用，以为氯吡格雷低反应的冠心病人群的中西医结合抗血小板治疗提供实验依据。

Clopidogrel is one of main clinical antiplatelet drugs. Clopidogrel low responsiveness (CLR) is an independent risk factor for cardiovascular events. P2Y12 receptor-mediated signaling pathways not only greatly affect clopidogrel reactivity, but maybe a potential therapeutic target of CLR. The effective compounds of rhizoma ligustici wallichii and radix paeoniae rubra, two important blood-activating and stasis-resolving herbs, have significant antiplatelet effects. Whether these two herbs play a role in improving CLR through regulating P2Y12 post-receptor signaling pathways has not yet been reported. Therefore, this study is designed to research the regulatory mechanism of the effective compounds of rhizoma ligustici wallichii and radix paeoniae rubra on CLR via in vitro experiment with the peripheral platelets taken from CLR group and healthy group. Besides, the study is also designed to research the impact of effective compounds of these two herbs on P2Y12 post-receptor signaling pathways at two respects (plaque stability and coronary microthrombosis) in apoE-knockout mice model with atherosclerosis and rat model with coronary microthrombosis, respectively. Taken together, the present study will provide experimental evidences of integrated Chinese-Western antiplatelet therapy for coronary heart disease patients with CLR.