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持续缺氧对闭环呼吸系统的影响及其动力学机制研究

INVESTIGATINT THE IMPACTS OF SUSTAINED HYPOXIA ON THE CLOSED-LOOP RESPIRATORY SYSTEM AND ITS DYNAMIC MECHANISMS

  • 摘要: 呼吸控制系统精确控制呼吸节律的生成和维持, 以适应机体在不同生理和病理状态下的需求. 当机体动脉血中的氧分压低于正常范围时, 可能引发病理性呼吸急促. Pre-Bötzinger复合体作为呼吸节律起源的关键部位, 其中包含呼气神经元、吸气神经元和跨时相神经元, 这些神经元通过神经调节和化学调节等多种机制协同工作, 共同调控呼吸节律. 呼吸过程涉及神经元网络的放电活动、肺泡的扩张与收缩、以及血液中氧气的传输等多个时间尺度的相互作用. 在一定的缺氧条件下, 闭环系统可以实现自我恢复. 本文主要研究在不同的初始放电状态时, 持续性缺氧干扰后系统的自我恢复能力. 研究结果表明, 系统的恢复情况可分为: 完全恢复至常氧水平、部分恢复至轻度缺氧水平或完全无法恢复. 基于方波电流的简洁性, 本研究简化了模型并应用动力学分析方法, 探讨了产生不同缺氧反应的动力学机制. 分岔分析表明, 系统在施加持续缺氧前、缺氧过程中、移除缺氧后以及再次达到稳定状态的各个阶段的分岔结构变化是影响系统恢复能力的关键因素, 并且只有缺氧前后分岔结构不发生改变的情形下, 系统才具备自我恢复至常氧的能力. 本研究增进了持续缺氧干扰对呼吸节律影响的理解, 研究节律恢复的外部因素和生理条件的联系, 以及节律恢复的内在动力学机制.

     

    Abstract: The respiratory control system precisely regulates the generation and maintenance of the breathing rhythm to adapt to the body's requirements in different physiological and pathological conditions. Pathological dyspnea can occur when oxygen levels in the arterial blood drop below the standard threshold. The pre-Bötzinger complex serves as a crucial site for the generation of the respiratory rhythm, contains expiratory neurons, inspiratory neurons, and post-inspiratory neurons. These neurons work in collaboration to regulate the respiratory rhythm through a variety of mechanisms, including neural modulation and chemical modulation. The breathing process involves interaction of multiple time scales, including the firing activity of neuronal networks, expansion and contraction of alveoli, and transport of oxygen in the blood. Understanding the mechanisms underlying the regulation of respiratory rhythm has long been a central focus of research. Under certain hypoxic conditions, the closed-loop respiratory control system exhibits self-recovery capabilities, as demonstrated in this study which investigates the system's self-recovery capability following sustained hypoxia interference under different initial conditions. The study demonstrates that the closed-loop respiratory control system can recover completely to normoxic level, partially recover to mild hypoxic level or completely fail to recover. Based on the simplicity of square wave currents, the study simplifies the closed-loop respiratory model and applies dynamic analysis methods to investigate the dynamic mechanisms of the system's different responses. Bifurcation analysis results indicate that changes of bifurcation structures at different stages during sustained hypoxia are key factors affecting the recovery capability. Specifically, the closed-loop respiratory control system can fully recover to normoxic level only when the bifurcation structure remain unchanged before and after sustained hypoxia, This research enchances our understanding of how sustained hypoxic perturbs respiratory rhythms, investigates the relationship between external factors and physiological conditions related to rhythm recovery, as well as the intrinsic dynamical mechanisms governing rhythm recovery.

     

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