血小板的凋亡与动脉粥样硬化（AS）密切相关。我们以往研究表明花色苷类植物化学物具有明显抑制AS的炎性反应、血小板活化聚集及血栓形成的效应，但花色苷对于血小板凋亡的调控缺乏研究。申请者近来的研究发现，花色苷对血小板线粒体凋亡通路及巨核细胞的分化成熟也具有调控作用,因此本研究拟在体外进一步明确花色苷对血小板线粒体凋亡的上下游通路中不同靶分子的影响及作用机制，探讨花色苷是否可以通过抑制BCL-2/BCL-XL 途径促进血小板的凋亡而抑制血小板的激活；利用ApoE-/-小鼠，研究花色苷在AS不同阶段对血小板凋亡、巨核细胞分化成熟和血小板生成的影响及其可能机制；并在高脂血症患者开展人群干预实验，观察花色苷对AS高危人群血小板凋亡标志物的影响。该研究将从细胞、动物和人群三个层次明确花色苷通过影响血小板凋亡而抑制AS的关键靶点及其分子机制，为进一步揭示花色苷类植物化学物防治AS的作用和机制提供科学依据。

Platelet apoptosis is involved in atherosclerotic development. In the applicant's lab, we have found that anthocyanins significantly inhibited platelet activation and aggregation, decreased platelet deposition and prolonged the occlusion time. However, the effects of anthocyanins on platelet apoptosis are poorly studied. Our primary data recently indicated that anthocyanins affect the platelet mitochondrial apoptotic pathway as well as the differentiation and maturation of megakaryocytes. Therefore, we will observe the detailed markers of the anthocyanins on the upstream and downstream intrinsic mitochondrial pathway of platelet apoptosis in the present study, and explore whether anthocyanins could disrupt platelet activation by BCL-2/BCL-XL inhibition during the apoptosis pathway. The ApoE-/- mice will be used to study the effects and mechanisms of anthocyanins on platelet apoptosis in the different stages of atherosclerosis (AS) as well as megakaryocyte differentiation, maturation and biogenesis of platelets in vivo. Furthermore, we will confirm the effects of anthocyanins on platelet apoptosis markers in dyslipidemic subjects whose diets will be supplied with anthocyanins capsules or placebo in a randomized,double-blind trial. Collectively, the study will demonstrate for the first time the effects and mechanisms of anthocyanins on platelet apoptosis, the differentiation and maturation of megakaryocyte in vitro and in vivo at the cell, animal and human level. Platelet apoptosis may be a feasible approach or target for preventing and treating for AS by anthocyanins.