Inhibitory effects of ethyl pyruvate on platelet aggregation and phosphatidylserine exposure
Inhibitory effects of ethyl pyruvate on platelet aggregation and phosphatidylserine exposure
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丙酮酸乙酯对血小板聚集和磷脂酰丝氨酸暴露的抑制作用
DOI：
10.1016/j.bbrc.2017.04.087
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发表时间：
2017-06-03
影响因子：
3.1
通讯作者：
Chen, Fangping
中科院分区：
文献类型：
--
作者：
Li, Wenjin;Yang, Xinyu;Chen, Fangping
丙酮酸乙酯（EP）是一种稳定的亲脂丙酮酸衍生物。研究表明，EP具有较强的抗氧化、抗炎和抗凝血作用。炎症和凝血与血小板活化密切相关。然而，EP是否具有抗血小板作用尚不清楚。因此，我们在体外研究了EP的抗血小板作用。我们发现EP抑制激动剂诱导血小板聚集、ATP释放和胶原粘附。流式细胞分析显示，EP抑制激动剂诱导的血小板PAC-1结合，以及p -选择素和CD40L的表达。潜在的作用机制可能涉及抑制血小板PI3K/Akt和蛋白激酶C （PKC）信号通路。此外，EP剂量依赖性地抑制高浓度凝血酶诱导的血小板PS暴露。乳酸脱氢酶（LDH）活性测定和小鼠血小板计数提示EP可能对血小板无毒性作用。因此，我们首次报道了EP在体外具有强大的抗血小板活性，并能减轻血小板PS暴露，提示EP对血小板的抑制作用也可能在相关动物模型中对炎症和凝血障碍的改善发挥重要作用。(C) 2017爱思唯尔公司版权所有。
Ethyl pyruvate (EP) is a stable lipophilic pyruvate derivative. Studies demonstrated that EP shows potent anti-oxidation, anti-inflammatory and anti-coagulant effects. Inflammation and coagulation are closely interacted with platelet activation. However, it is unclear whether EP has anti-platelet effects. Therefore, we investigated the anti-platelet effect of EP in this study in vitro. We found that EP inhibited agonists induced platelets aggregation, ATP release and adhesion to collagen. Flow cytometric analysis revealed that EP inhibited agonist induced platelets PAC-1 binding, as well as P-selectin and CD40L expression. The underlying mechanism of action may involve the inhibition of platelet PI3K/Akt and Protein Kinase C (PKC) signaling pathways. Additionally, EP dose dependently inhibited platelet PS exposure induced by high concentration thrombin. Lactate dehydrogenase (LDH) activity assay and mice platelet count implied that EP may have no toxic effect on platelets. Therefore, we are the first to report that EP has potent anti-platelet activity and attenuates platelet PS exposure in vitro, suggesting that the inhibitory effects of EP on platelets may also play important roles in improvement of inflammation and coagulation disorder in related animal models. (C) 2017 Elsevier Inc. All rights reserved.