CD36/NOX2介导的信号通路在莱菔硫烷调控高脂血症血小板功能和防治血栓形成的作用及其机制研究

高脂血症导致的血栓形成是心血管疾病致死的首要原因，研究表明血小板CD36/NOX2信号轴在高脂血症中氧化低密度脂蛋白(ox-LDL)诱导的血小板过度激活进而导致血栓形成中起关键作用。植物化学物莱菔硫烷(SFN)具有改善糖脂代谢紊乱，防治心血管疾病的作用，本项目前期发现SFN可抑制ox-LDL诱导的血小板活化和聚集。我们据此推测：SFN可能通过下调CD36/NOX2信号轴，降低ox-LDL所致的血小板高反应性，从而抑制血栓形成。本研究首先拟在体外实验继续深入探讨SFN对ox-LDL-CD36/NOX2上下游通路中不同靶分子的影响及作用机制；然后利用高脂血症ApoE-/-小鼠，探讨膳食补充SFN经CD36/NOX2轴调控高脂血症小鼠血小板功能和血栓形成的影响和作用机制。该研究将从体外和动物研究两个层面，阐明SFN经血小板CD36/NOX2轴防治高脂血症及其他相关心脑血管疾病血栓形成的调控机制。

Thrombosis caused by hyperlipidemia is recognized as the leading cause of mortality from cardiovascular diseases. Previous researches have demonstrated that CD36/NOX2 signaling plays pivotal roles in oxidized low-density lipoprotein (ox-LDL)-induced platelet hyper-reactivity and thrombus formation during hyperlipidemia. Sulforaphane (SFN), a type of natural plant pigment, has been shown to improve disorder of glucose-lipid metabolism and cardiovascular diseases. Our former experiments have demonstrated that SFN attenuates ox-LDL-induced platelet activation and aggregation. Therefore, we hypothesize that SFN attenuates ox-LDL-induced platelet hyper-reactivity maybe through down-regulating CD36/NOX2 signaling pathway, and thus inhibiting thrombus formation. The present research intends to further study the effects and mechanisms of SFN on CD36/NOX2 signaling pathway in platelets that activated by ox-LDL in vitro. In the 2nd part of study, we establish a hyperlipidemic mice model using ApoE−/− mice fed on a high-fat diet, and then determine whether the inhibitory effects of dietary SFN supplements on platelet hyper-reactivity and thrombus formation is involved in its attenuation of CD36/NOX2 signaling pathway in hyperlipidemic mice. Collectively, this study will demonstrate important roles of platelet CD36/NOX2 signaling pathway in the anti-thrombotic effect of SFN supplementation during hyperlipidemia and the related cardio-cerebro-vascular diseases.