活血解毒中药成分配伍调控LDLR-/-动脉粥样硬化仓鼠血小板活化及嘌呤能受体信号通路的研究

The pathological basis of cardiovascular events in coronary heart disease is the rupture of unstable atherosclerosis plaque and thrombosis, and the key aspect of the formation of coronary artery thrombosis is platelet activation. Thus, to explore the effect and molecular mechanism of traditional Chinese medicine for activating blood circulation and detoxifying (ABCD) of stabilizing plague through platelet activation is of great importance for the prevention of cardiovascular events in coronary heart disease. Previous studies have shown that the antiplatelet effect of ABCD Chinese medicine is related to the inhibition of p2urine receptor pathways. LDLR KO hamster is a new animal model of AS obtained from CRISPR/CAS9 skills, which is similar to human being. On the basis of previous work, we further explore the effect of ABCD Chinese medicine on platelet activation and atherosclerotic plaques to identify the molecular mechanism involving in the p2urine receptor pathways and provide experimental evidence and molecular targeting for the usage of traditional Chinese medicine.

冠心病心血管事件发生的病理基础为动脉粥样硬化（AS）不稳定斑块糜烂、破裂继发血栓形成，诱发AS斑块破裂一个关键病理环节是血小板活化。因此，从血小板活化深化研究活血解毒中药稳定AS斑块的分子机理，对预防冠心病心血管事件有重要意义。课题组前期研究发现，活血解毒中药抗血小板作用与抑制嘌呤能受体信号通路密切相关。LDLR-/-仓鼠是通过CRISPR/CAS9基因编辑技术获得的新型AS动物模型，其脂质代谢过程与人类相似，可通过高脂饮食诱导冠状动脉粥样硬化不稳定斑块形成。本课题采用此模型，观察活血解毒中药配伍稳定AS斑块、调节脂质代谢的效应，以嘌呤能受体信号转导通路为切入点，探讨其抗血小板活化和稳定动脉粥样硬化斑块的相关分子机理，可望为中药防治AS不稳定斑块继发血栓形成提供可靠的实验依据。

冠心病心血管事件发生的病理基础为动脉粥样硬化（AS）不稳定斑块糜烂、破裂继发血栓形成，诱发AS斑块破裂一个关键病理环节是血小板活化。因此，从血小板活化深化研究活血解毒中药稳定AS斑块的分子机理，对预防冠心病心血管事件有重要意义。课题组前期研究发现，活血解毒中药抗血小板作用与抑制嘌呤能受体信号通路密切相关。本研究利用LDLR-/-地鼠通过高脂饮食诱导建立动脉粥样硬化模型。基于此模型的实验结果显示活血解毒中药组分配伍（黄连素+川芎嗪）可延缓动脉粥样硬化进展，其机制可能与抑制血小板活化的信号传导通路有关。本研究探讨了活血解毒中药组分配伍（黄连素+川芎嗪）抗血小板活化和稳定动脉粥样硬化斑块的相关分子机理，可望为中药防治AS不稳定斑块继发血栓形成提供可靠的实验依据