Cer—SPK—S1P通路在动脉粥样硬化中的作用及田黄片的干预研究

项目名称： Cer—SPK—S1P通路在动脉粥样硬化中的作用及田黄片的干预研究

项目编号： No.81503313

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 罗朵生

作者单位： 广东药科大学

项目金额： 18万元

中文摘要： 动脉粥样硬化（AS）发病率高、危害大，目前临床一线治疗药物为针对低密度胆固醇合成的他汀类药物，仅能降低急性冠脉事件30%左右，急需寻找更有效的防治药物和作用靶点。田黄片（THP）为临床验方制剂，前期研究显示其具有改善血脂谱、防治脂肪肝、抑制动脉粥样硬化形成及抗氧化等综合作用，获得了专利保护，具良好应用前景。新近代谢组学研究又发现其还具有降低血鞘磷脂（SM），升高1-磷酸鞘氨醇（S1P）作用。那么，在其抑制巨噬细胞泡沫化，调节血脂代谢、抗氧化能力等机制外，调节SM、S1P是否是其抗AS又一新机制？鞘氨醇激酶（SPK）作为调控 SM与 S1P 代谢平衡的关键酶，在动脉粥样硬化中扮演什么角色？本课题拟将细胞实验与动物实验相结合，揭示SPK在AS中的关键作用，阐明THP抗AS作用新机制，为临床有效干预AS提供优质候选药物和潜在生物靶标，拓展AS防治思路和视野。

中文关键词： Cer—SPK—S1P通路；田黄片；动脉粥样硬化；作用机制

英文摘要： Atherosclerosis (AS) is a common disease with high morbidity and mortality. The current clinical first-line drug for AS is statins, which can reduce only about 30% of acute coronary events by inhabiting LDL cholesterol synthesis. Therefore more effective drugs and targets are necessarily to be developed. Preliminary studies showed that THP, a proved recipe of Chinese Medicine, had the comprehensive effects of anti-atherosclerosis, improving lipid profile, inhibiting macrophage foaming and antioxidant. Subsequently THP got the patent protection, and had good prospects. The latest metabolomics study investigated that THP could decrease blood sphingomyelin (SM) and increase 1- sphingosine phosphate (S1P). Then whether regulation of SM and S1P is an alternative pathway of anti-atherosclerosis? What about the role of the key enzyme of sphingosine kinase (SPK) which regulating the metabolism of SM and S1P in the AS pathophysiology? This study intends to reveals key role of SPK in AS developing, clarify anti-atherosclerotic mechanism of THP , both in vivo and in vitro,to threw lights in the development of high quality candidate drug and potential biological targets.

英文关键词： Cer—SPK—S1P pathway;TianHuang Pian ;atherosclerosis;mechanism