下丘脑-垂体-肾上腺轴动力学的数学建模：综述、一种新方法与未来
Mathematical Modelling of Hypothalamus-Pituitary-Adrenal Axis Dynamics: A Review, a Novel Approach, and Future
AI总结：
本文提出整合海马受体、AVP通路、昼夜节律和短负反馈的HPA轴新数学模型，提升了皮质醇等激素动力学的预测与拟合精度。
摘要：
本文提出了一种新的下丘脑-垂体-肾上腺（HPA）轴数学模型，以理解在应激情境下观察到的激素浓度振荡以及HPA轴内潜在的功能障碍。该模型在一个最小机制型HPA轴模型中整合了以下内容：海马受体对促肾上腺皮质激素释放激素（CRH）分泌的影响；一条涉及精氨酸加压素（AVP）的额外信号通路，用于促肾上腺皮质激素（ACTH）的生成与分泌；纳入一个与日光相关的函数以模拟昼夜节律；以及一条从垂体到下丘脑的短负反馈回路。这一扩展使我们能够估计模型参数，从而显著降低平均绝对百分比误差，提高模型的预测准确性，并证明其对验证数据集具有很强的拟合度。通过敏感性分析和相关性分析，本研究展示了对系统内皮质醇动力学影响最显著的参数。研究揭示了模型内部以及HPA轴各组成部分之间复杂的相互依赖关系。尽管当前模型在理解HPA轴动力学方面取得了进展，但这些模型在处理一些主要因素方面仍有不足，例如遗传和表观遗传的影响、杏仁核在处理和传递应激信号中的作用，以及其他次要影响因素。
英文摘要：
A novel mathematical model for the hypothalamic pituitary adrenal (HPA) axis is proposed to comprehend the oscillations observed in hormone concentration and potential dysfunction within the HPA axis in stressful situation. This model integrates impact of hippocampal receptors on the secretion of corticotropin-releasing hormone (CRH), an additional signaling pathway involving Arginine Vasopressin (AVP) for the production and secretion of adrenocorticotropic hormone (ACTH), the inclusion of a daylight-related function for modeling circadian rhythms, and a short negative feedback loop from the pituitary to the hypothalamus in a minimal mechanistic model of the HPA axis. This expansion allows us to estimate model parameters that led to a significant reduction in the mean absolute percent error, thereby enhancing the model's predictive accuracy with a demonstration of a strong fit to the validation dataset. Through sensitivity and correlation analyses, our study shows the parameters that exert the most significant influence on the dynamics of cortisol within the system. This study reveals intricate interdependencies within the model and among the various components of the HPA axis. Despite current advancements in the model to comprehend the dynamics of the HPA Axis, these models are still lacking in addressing major factors such as the impact of genetic and epigenetics, the role of the amygdala in processing and transmitting stress signals, and other minor impacting factors.
机构、总结、中文摘要均由AI分析而来，可能存在错误，请以论文正文为准。
