动脉粥样硬化(AS)是慢性炎症过程，血小板在此过程中发挥重要作用，被激活后释放促炎趋化因子，招募白细胞等到达炎症部位促进斑块形成。我们以往研究表明花色苷有抑制血小板活化聚集及血栓和抗炎等效应，但其对血小板趋化因子的调控及机制缺乏研究。我们近来发现，花色苷在体内和体外均显著抑制高脂血症患者血小板趋化因子CXCL7、CCL5等的释放，故本研究拟利用高脂饲料喂饲的ApoE-/-小鼠，首先在体内明确花色苷对小鼠纯化血小板分泌的趋化因子的影响，重点探讨花色苷是否通过抑制CXCL7的受体整合素信号通路而调控白细胞的激活黏附迁移等功能及斑块形成，从而在明确花色苷对血小板趋化因子和AS炎症的体内调控效应。该研究将从动物水平明确花色苷通过调控血小板趋化因子及白细胞相互作用而抑制AS炎症的关键靶点及机制，为揭示花色苷防治AS提供科学依据。

Atherosclerosis (AS) is a chronic inflammatory disease, and activated platelets has been recognized to play an essential function in the development of atherosclerosis. Platelets are the source of chemokines which are well known to be the consequence of pro-inflammatory mediators stored in platelets and released during atherosclerosis, efficiently attract leukocytes to the site of inflammation. Therefore, chemokines released by platelets play a crucial role in atherosclerosis via their strong potency to attract circulating inflammatory cells. In the applicant's lab, we have found that anthocyanins significantly inhibited inflammation, platelet activation and aggregation, decreased platelet deposition and prolonged the occlusion time in AS. However, the effects of anthocyanins on platelet-derived chemokines are poorly studied. Our primary data recently indicated that anthocyanins affect significantly the highly specific platelet-derived chemokines of patients with hyperlipidemia, such as CXCL7 and CCL5 both in vitro and in vivo. Therefore, the ApoE-/- mice fed with high fat diet will be used to observe the detailed markers of the different platelet-derived chemokine treated by anthocyanins in the present study, and explore whether anthocyanins could disrupt or decrease leukocyte recruitment to the site of inflamed endothelium via prohibiting the release of platelet-derived chemokines, blocking CXCL7 receptor CXCR1/R2 and activating its integrin Mac-1 to its platelet ligands as well, we also will study the effects and mechanisms of anthocyanins on platelet-derived chemokines in the different stages of AS as well as leukocyte recruitment, adhesion, migration to injured endothelial surfaces and leads to a reduction of atherosclerotic lesions in vivo. Collectively, the study will demonstrate for the first time the effects and mechanisms of anthocyanins on platelet-derived chemokines, the interactions of the different chemokines produced by platelets participate in leukocyte functions in vivo at the animal level. The highly specific platelet-derived chemokines may be a feasible approach or target for preventing and treating AS by anthocyanins.