剪切流下VWF-A1介导的血小板钙响应
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国家自然科学基金项目(11672109, 11432006,11272125),中央高校专项基金(华南理工大学D2156960)


VWF-A1-Mediated Calcium Response of Platelets under Shear Flow
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    摘要:

    目的 探讨血流剪切率和VWF-A1偶联介导的血小板钙响应。方法 以Flou-4 AM为胞内钙离子的荧光指示剂,结合平行平板流动腔实验系统和荧光显微镜,实时观测血小板在不同剪切率下流经不同浓度VWF-A1底板滚动、黏附后胞内钙离子浓度的变化。分析力、化学信号对钙响应强度及快慢的影响。结果 在流场条件下,VWF-A1可特异性介导血小板的黏附并发生钙响应。血流剪切率和底板分子浓度正向调节血小板的激活比率,反向调节钙响应的延迟时间。剪切率500 s-1时激活比率是静息条件下的37倍。底板VWF-A1的浓度从60 mg/L提高到240 mg/L,钙响应延迟时间缩短10 s。结论 血流剪切率和VWF-A1协同调控血小板的钙响应。研究结果有助于深化对血流环境下血小板凝血止血反应过程的理解。

    Abstract:

    Objective To investigate the shear rate and VWF-A1-mediated platelets calcium response. Methods Flou-4 AM was used as the fluorescent indicator of intracellular calcium, and the intracellular calcium concentrations of adherent platelets on VWF-A1 with different concentrations at different shear rates were detected by parallel plate flow chamber system combined with fluorescence microscope. The effect of shear stress and chemical signaling on intensity and speed of calcium response was also analyzed. Results VWF-A1 specifically mediated platelet adhesion and calcium response under flow. The shear rate and molecular concentrations had positive regulation of platelets activation ratio and negative regulation of delay time of calcium response. Compared with static conditions, the activation ratio was increased by 37 times at shear rate of 500 s-1. When the concentration of VWF-A1 was increased from 60 mg/L to 240 mg/L, the delay time of calcium response was shortened by 10 s. Conclusions The shear rate could modulate the calcium response of platelets in cooperation with VWF-A1. The result of this study will be helpful to deepen the understanding about the process of hemostatic reaction of platelet coagulation in bloodstream.

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高绪强,刘晓玲,吴建华,方颖.剪切流下VWF-A1介导的血小板钙响应[J].医用生物力学,2019,34(1):83-90

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  • 收稿日期:2018-02-10
  • 最后修改日期:2018-03-26
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  • 在线发布日期: 2019-03-01
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