血小板表达活性P2Y12受体在糖尿病患者中
Liang Hu1, Lin Chang1, Yan Zhang1
1From Key Laboratory of Metabolism and Molecular Medicine, Ministry of Education, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, China (L.H., L.C., Y.Z., L.Z., Shenghui Z., Si Z., Z.D.); Division of Cardiovascular Disease (Z.Q.), Division of Endocrinology and Metabolism (H.Y.), Huashan Hospital, Fudan University, Shanghai, China; Department of Endocrinology and Metabolism (H.Y.), Division of Cardiovascular Disease (Y.Y.), Zhongshan Hospital, Fudan University, Shanghai, China; Department of Pharmacology I, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China (L.H., Y.W.); Department of Physiology and Sol Sherry Thrombosis Research Center, Temple University School of Medicine, Philadelphia, PA (S.P.K.). Dr Shenghui Zhang is presently at Department of Hematology, Wenzhou Key Laboratory of Hematology, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
2型糖尿病患者的血小板具有较高的P2Y12受体水平和活性,导致过度活跃. 这解释了一些抗血小板药物在糖尿病患者中的有效性降低.
科学领域:
- 心血管研究
- 血液学
- 内分泌学
背景情况:
- 糖尿病患者的血小板显示过度活跃,可能导致心血管问题和对抗血小板治疗的反应不佳.
- 在糖尿病中血小板过活的确切机制尚不清楚.
研究的目的:
- 研究糖尿病血小板中的P2Y12受体表达和激活.
- 在糖尿病模型中比较不同P2Y12抑制剂的疗效.
- 探索核因子-卡帕B (NF-κB) 途径在P2Y12表达的调节中的作用.
主要方法:
- 在2型糖尿病患者和老鼠的血小板中测量P2Y12表达和激活 (cAMP,VASP酸化).
- 在老鼠中比较AR-C78511和康格洛尔的抗血小板和抗血栓作用.
- 研究了NF-κB通路在巨核细胞P2Y12调节中的作用.
主要成果:
- 糖尿病患者的血小板P2Y12水平高出4倍,与聚合相关.
- 在糖尿病血小板中,P2Y12受体具有构成性活性.
- 在糖尿病模型中,AR- C78511的抗血小板和抗血栓作用优于康格洛.
- 一个涉及高葡萄糖,ROS和NF-κB的途径增加了糖尿病中的P2Y12表达.
结论:
- 在2型糖尿病中,P2Y12受体的增加和活性有助于血小板过活.
- 在糖尿病中P2Y12受体表达和活性升高限制了某些抗血小板药物的疗效.
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