乳酸代谢在血小板活化及血栓形成中的作用及机制研究

我们的前期研究数据显示血小板可产生大量乳酸，并且乳酸脱氢酶缺乏（Ldha-/-）明显抑制了血小板的体外聚集能力。这一结果表明乳酸代谢可能在血小板活化过程中起着非常重要的作用。本项目计划利用巨核细胞/血小板特异Ldha基因敲除小鼠、代谢流分析技术、多种细胞及生物化学手段，结合多种小分子抑制剂，揭示造成血小板产生大量乳酸的原因；阐明乳酸代谢调控血小板活化与血栓形成的基本机制；揭示血小板乳酸代谢在整个机体乳酸稳态中的作用；研究结果将丰富血小板活化的调控机制理论并为抗血小板药物开发提供新的靶点，因此具有重要的科学意义及应用价值。

Our previous data showed that platelet produced large amounts of lactate, and lactate dehydrogenase A deficiency (Ldha-/-) significantly inhibited agonists-induced platelet aggregation in vitro. The results suggested that lactate metabolism play important roles in platelet activation. In this project, using megakaryocyte/platelet specific Ldha gene knock out mice, metabolic flow analysis technology, cellular and biochemical technologies, combining with specific inhibitors, we plan to find out why platelets produce so much lactate, to reveal the mechanism of lactate metabolism in platelet activation and thrombosis, and the role of platelet in maintaining lactate homeostasis. The findings will enrich the regulation mechanism of platelet activation and provide new targets for the development of anti-platelet drugs.