氯吡格雷抵抗(CR)是卒中防治的热点和难点。传统活血化瘀中药对CR有一定干预作用，但其机制尚不清楚。申请人前期研究发现CR患者联用大黄蛰虫丸后血小板聚集有明显下降(P=0.028)，提示大黄蛰虫丸有协同抗血小板作用。进一步研究发现大黄蛰虫丸可下调血小板P2Y12受体的表达，亦可抑制泛素蛋白Ub合成进而阻断UPP/NF-κB信号通路。考虑到激活NF-κB能上调P2Y12受体表达，我们推测大黄蛰虫丸可能通过抑制UPP/NF-κB信号通路上游Ub合成，阻断下游P2Y12受体表达，从而与P2Y12受体拮抗剂氯吡格雷发挥协同抗血小板作用。为此，本课题拟采用VerifyNow血小板功能分析仪明确大黄蛰虫丸的抗血小板作用，并同步检测UPP/NF-κB信号通路上下游关键信号分子进而验证上述假说。上述研究有望揭示大黄蛰虫丸抗血小板机制，有望建立抗栓药物疗效评价体系，为中西医结合抗栓治疗提供新靶点和科学依据。

Clopidogrel resistance (CR) is a hot and difficult issue in the prevention and treatment of stroke. Traditional Chinese medicine for promoting blood circulation and removing blood stasis has some effect on CR, but its mechanism is still unclear. In our preliminary study, we found a significant decrease in platelet aggregation in CR patients treated with Dahuang Zhechong Wan (P=0.028), which mean Dahuang Zhechong Wan had a combined antiplatelet effect with clopidogrel. Dahuang Zhechong Wan was found to have the function of not only down-regulating the expression of ADP receptor P2Y12, but also blocking the UPP/NF-κB pathway by inhibiting ubiquitin protein Ub in previous research. Considering the activation of nuclear factor-κB (NF-κB) can up-regulate the expression of P2Y12 receptor, we hypothesize that Dahuang Zhechong Wan may inhibit the synthesis of ubiquitin protein Ub, the upstream signal of the UPP/NF-κB pathway, which can cause the expression of downstream P2Y12 receptor blocked. Thus, Dahuang Zhechong Wan has synergistic antiplatelet effect with the P2Y12 receptor antagonist clopidogrel. This project intends to use the advanced platelet function analyzer VerifyNow to detect the antiplatelet effect of Dahuang Zhechong Wan, and verify the previous hypothesis by detecting the upstream and downstream key signal molecules of the UPP/NF-κB pathway. The above study is expected to reveal the antiplatelet mechanism of Dahuang Zhechong Wan, and to establish the efficacy evaluation system of antiplatelet drugs, which may provide a new target and scientific basis for the antiplatelet therapy of integrated traditional Chinese and western medicine.