学术论文

      柚皮素通过PI3K/Akt通路拮抗血小板聚集的体外研究

      Antiplatelet aggregation of naringenin via inhibiting PI3K/Akt signaling in vitro

      摘要:
      目的:探讨柚皮素拮抗二磷酸腺苷(ADP)诱导的血小板聚集的作用及机制.方法:采用血小板聚集仪观察不同浓度柚皮素对ADP诱导的大鼠血小板聚集的影响.采用荧光显微镜观察柚皮素对血小板在固化纤维蛋白原上扩展功能的影响.采用Western blot检测磷脂酰肌醇3-激酶(PI3K)表达及蛋白激酶B(Akt)磷酸化水平.结果:柚皮素能剂量依赖性地抑制ADP诱导的体外血小板聚集,其半数抑制浓度(IC50)值为(132.1±31.7)μmol/L.柚皮素灌胃给药,对ADP诱导的大鼠体内血小板聚集也有明显的抑制作用.柚皮素还能显著抑制血小板在固化纤维蛋白原上的扩展.Western blot结果显示,柚皮素能明显抑制ADP刺激的PI3K表达和Akt磷酸化,同时,PI3K广谱抑制剂LY294002能增强柚皮素对Akt磷酸化的抑制作用.结论:柚皮素可能通过抑制血小板PI3K/Akt信号通路发挥抗血小板聚集的作用.
      Abstract:
      AIM: To investigate the antiplatelet aggregation of naringenin and its possible mechanism . METHODS:The effects of naringenin at different concentrations on adenosine diphosphate ( ADP)-induced platelet aggre-gation and platelet spreading on immobilized fibrinogen were detected by aggregational detector and observed under fluores -cence microscope, respectively.The expression of phosphoinositide 3-kinase (PI3K) and the phosphorylation of Akt were analyzed by Western blot .RESULTS:Naringenin significantly inhibited ADP-induced platelet aggregation in a dose-de-pendent manner in vitro and in vivo, and inhibited platelet ' s spreading on immobilized fibrinogen in vitro.Further studies indicated that naringenin inhibited platelet activation accompanied by attenuating not only the activation of PI 3K, but also the phosphorylation of Akt .Moreover, naringenin combined with LY294002 additively inhibited the ADP-induced platelet aggregation.CONCLUSION:Naringenin may inhibit platelet activation by regulation of PI 3K/Akt signaling pathway.
      作者: 黄曼婷 [1] 吴焕林 [2] 徐丹苹 [2]
      Author: HUANG Man-ting [1] WU Huan-lin [2] XU Dan-ping [2]
      作者单位: 广州中医药大学第二临床医学院,广东广州,510020 广东省中医院,广东广州,510020
      刊 名: 中国病理生理杂志 ISTICPKU
      年,卷(期): 2017, 33(3)
      分类号: R363
      在线出版日期: 2017年4月10日
      基金项目: 国家自然科学基金资助项目,广东省中医药管理局科技专项,广东省科技计划项目