标题： 血小板在人体中的正常和病理动力学 显示英文标题

标题： Normal and pathological dynamics of platelets in humans

摘要： 我们开发了一个关于人类血小板、巨核细胞和血小板生成素动态的综合性数学模型。 我们表明存在一个单一的稳态解，可以发生霍普夫分支，并利用这一信息来研究正常和病理性的血小板生成，特别是周期性血小板减少症。 通过仔细估计实验室和临床数据中的模型参数，我们随后认为基于临床信息，部分参数参与了周期性血小板减少症的形成。 通过改变六个具有生理相关性的参数，我们提供了对现有血小板计数和血小板生成素水平数据的良好模型拟合。 我们的结果表明，周期性血小板减少症的主要变化是血小板生成素受体的重大干扰或破坏，以及在其他过程中的次级变化，包括免疫介导的血小板破坏和巨核细胞缺乏以及血小板生成失败。 这项研究对理解周期性血小板生成素的起源做出了重大贡献，并显著扩展了血小板生成的建模。 显示英文摘要

摘要： We develop a comprehensive mathematical model of platelet, megakaryocyte, and thrombopoietin dynamics in humans. We show that there is a single stationary solution that can undergo a Hopf bifurcation, and use this information to investigate both normal and pathological platelet production, specifically cyclic thrombocytopenia. Carefully estimating model parameters from laboratory and clinical data, we then argue that a subset of parameters are involved in the genesis of cyclic thrombocytopenia based on clinical information. We provide excellent model fits to the existing data for both platelet counts and thrombopoietin levels by changing six parameters that have physiological correlates. Our results indicate that the primary change in cyclic thrombocytopenia is a major interference with or destruction of the thrombopoietin receptor with secondary changes in other processes, including immune-mediated destruction of platelets and megakaryocyte deficiency and failure in platelet production. This study makes a major contribution to the understanding of the origin of cyclic thrombopoietin as well as significantly extending the modeling of thrombopoiesis.