Platelet-driven routes to chaos in a model of hepatitis
Platelet-driven routes to chaos in a model of hepatitis
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肝炎模型中血小板驱动的混乱途径
DOI：
10.1016/j.chaos.2023.113338
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Nelson M
中科院分区：
文献类型：
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作者：
Nelson M
肝炎是一个通用的术语，用于描述肝脏的炎症，其调节涉及肝细胞、炎症介质和免疫系统细胞(特别是巨噬细胞和中性粒细胞)之间一系列复杂的相互作用。越来越多的证据表明，血小板(主要负责凝血的小血细胞)会影响肝炎背后的许多机制，包括细胞迁移、肝脏损伤和介质产生的速度，从而导致一系列复杂和多样化的炎症结果。特别是，血小板激活有可能以一种高度不可预测和潜在的状态依赖的方式促进健康和慢性结果，目前还没有被很好地理解。在本文中，我们采用了与肝炎相关的炎症动力学的现有模型，并介绍了血小板及其作用。我们通过MatLab中的数值模拟和XPPAUT中的分叉分析来询问这个新模型，发现血小板对某些关键相互作用的放大可以刺激对应于复杂慢性结果的混沌动力学。我们最初引入一个参数来表示血小板刺激的规模，并通过分叉分析说明，随着该参数的逐渐增加，我们看到了导致混沌动力学的倍周期级联的出现。然后，我们更详细地探索个别机制，并说明，虽然中性粒细胞在某些环境中可以促进混乱，但导致混乱的途径主要是由巨噬细胞相关的血小板刺激驱动的。最后，我们简要地评论了我们的观察结果对正在寻找新的肝炎治疗干预措施以及其他与炎症相关的医疗条件的影响。
Hepatitis is a general term used to describe inflammation in the liver, the regulation of which involves a complex array of interactions between liver cells, inflammatory mediators and cells of the immune system (macrophages and neutrophils, in particular). There is increasing evidence that platelets (small blood cells that are primarily responsible for clotting) affect numerous mechanisms that underlie hepatitis, including the rates of cell migration, liver damage and mediator production, giving rise to a complex and diverse range of inflammatory outcomes. In particular, platelet activation has the scope to promote both healthy and chronic outcomes in a highly unpredictable and potentially state-dependent manner that is not currently well-understood. In this paper, we take an existing model of the inflammatory dynamics associated with hepatitis, and introduce platelets and their effects. We interrogate this new model via numerical simulations in Matlab and bifurcation analysis in XPPAUT, and find that amplification of certain key interactions by platelets can stimulate chaotic dynamics that correspond to complex chronic outcomes. We initially introduce a single parameter to represent the scale of the platelet stimulus and, through bifurcation analysis, illustrate that as this parameter is gradually increased we see the emergence of a period-doubling cascade that results in chaotic dynamics. We then explore individual mechanisms in more detail and illustrate that, while neutrophils can promote chaos in some settings, routes to chaos are primarily driven by macrophage-related platelet stimuli. Finally, we briefly comment upon the implications of our observations in terms of the ongoing hunt for new therapeutic interventions in hepatitis, as well as other inflammation-related medical conditions.