Xinmailong Modulates Platelet Function and Inhibits Thrombus Formation via the Platelet αIIbβ3-Mediated Signaling Pathway
Xinmailong Modulates Platelet Function and Inhibits Thrombus Formation via the Platelet αIIbβ3-Mediated Signaling Pathway
复制标题
心脉隆通过血小板αIIbβ3介导的信号通路调节血小板功能并抑制血栓形成
DOI：
10.3389/fphar.2019.00923
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发表时间：
2019-08-23
影响因子：
5.6
通讯作者：
Meng, Zhaohui
中科院分区：
文献类型：
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作者：
Wang, Huawei;Ye, Yujia;Meng, Zhaohui
背景：新脉龙是一种从美洲大蠊中提取的生物活性复合物，已被广泛用于治疗充血性心力衰竭等心血管疾病。然而，XML是否具有抗血小板和抗血栓作用尚不清楚。方法：观察XML对激动剂诱导的血小板聚集、粘附和扩散、颗粒分泌、整合素α II b β 3活化和血栓形成的影响。我们还研究了Syk、PLC γ 2、Akt、GSK3 β和MAPK信号分子在激动剂诱导的血小板上的磷酸化。此外，在小鼠急性肺血栓模型中观察了XML的抗血栓作用。结果：XML对凝血酶、胶原蛋白和花生四烯酸诱导的体外血小板聚集和颗粒分泌具有剂量依赖性。XML还大大减少了血小板在胶原蛋白和纤维蛋白原包被表面的粘附和扩散。生化分析显示，XML抑制凝血酶、胶原蛋白和aa诱导的Syk、PLC γ 2、Akt、GSK3 β和MAPK的磷酸化。此外，在胶原肾上腺素诱导的急性肺血栓小鼠模型中，XML显著抑制体内血栓形成。结论和一般意义：在这里，我们提供了第一个报告，显示XML抑制血小板功能，并具有抗血栓活性。这表明XML可能是预防或治疗血小板相关心血管疾病的潜在治疗候选者。
Background: Xinmailong (XML), a bioactive composite extracted from Periplaneta americana, has been widely used to treat cardiovascular diseases such as congestive heart failure. However, it is unclear whether XML has antiplatelet and antithrombotic effects.Methods: The effects of XML on agonist-induced platelet aggregation, adhesion and spreading, granule secretion, integrin alpha II b beta 3 activation, and thrombus formation were evaluated. Phosphorylation of Syk, PLC gamma 2, Akt, GSK3 beta, and MAPK signaling molecules was also studied on agonist-induced platelets. In addition, the antithrombotic effects of XML were observed in vivo using an acute pulmonary thrombosis mouse model.Results: XML dose-dependently inhibited in vitro platelet aggregation and granule secretion induced by thrombin, collagen, and arachidonic acid (AA). XML also greatly reduced platelet adhesion and spreading on both collagen- and fibrinogen-coated surfaces. Biochemical analysis revealed that XML inhibited thrombin-, collagen-, and AA-induced phosphorylation of Syk, PLC gamma 2, Akt, GSK3 beta, and MAPK. Additionally, XML significantly inhibited in vivo thrombus formation in a collagenepinephrine-induced acute pulmonary thrombosis mouse model.Conclusions and General Significance: Here, we provide the first report showing that XML inhibits platelet function and that it possesses antithrombotic activity. This suggests that XML could be a potential therapeutic candidate to prevent or treat platelet-related cardiovascular diseases.