声音闭环刺激在心衰合并失眠者自主神经功能调控中的作用

Insomnia is highly prevalent in patients with heart failure (HF), and it can exacerbate the progression and mortality of HF, leading to poorer life quality and worse prognosis. However, there is currently lack of practical and effective intervention approaches in clinic, the conventional drugs for the treatment of HF will increase insomnia, and sedative and hypnotic drugs will increase the risk of addiction, cardiac arrest and respiratory depression. Therefore, it is imperative to develop new non-drug intervention strategies. Previous studies have shown that the hyperarousal state of insomnia is closely related to the dysfunction of autonomic nerve system (ANS), and the dysfunction of ANS plays a key role in the development of HF, but its exact neural mechanism remains unclear. Therefore, this study intends to systematically characterize the peripheral ANS activity in HF patients with insomnia and explore its possible underlying brain mechanisms by multi-modal neural monitoring, and restore the balance of ANS activity and improve the symptoms of HF through regulation of brain function with non-invasive auditory closed-loop stimulation during sleep. This study will substantially increase our understanding of mechanisms underlying negative feedback loop between HF and insomnia, which in the long term may aid in the development of novel therapeutic interventions to the HF patients.

心衰（HF）患者中普遍存在失眠问题，失眠能够加速HF的进展及死亡，严重影响患者的生活质量及长期预后。但目前临床尚缺乏有效的干预手段，传统的心衰治疗药物会加重失眠，而镇静催眠药物又会导致成瘾、心脏骤停及呼吸抑制的风险增加。因此，非常有必要开发新型非药物干预策略。已有研究表明，失眠导致的高觉醒状态与外周自主神经系统（ANS）功能失调有关，而外周ANS功能失调在心衰进展中发挥关键作用，但其确切的神经机制目前尚不清楚。因此，本项目拟通过多模态神经监测技术系统性探索心衰合并失眠者外周ANS功能活动特征及潜在的神经机制，同时结合非侵入闭环神经调控手段，通过干预患者的夜间睡眠脑功能活动，从而达到恢复外周ANS功能平衡及改善心衰症状的目的。该研究将有助于深入理解失眠参与心衰进展的机制，同时也为心衰患者的治疗提供新型非药物干预手段。

失眠与心衰的发生和进展密切相关，失眠会导致心衰的发生和症状的恶化，而心衰症状的恶化又往往会加重失眠问题。本研究主要采用行为学、多导生理记录及多模态神经监测等技术研究心衰合并失眠者外周自主神经功能活动特征及其潜在脑功能机制。主要研究内容包括：1）明确心衰合并失眠者外周自主神经 ANS 功能活动特征及其潜在脑功能机制；2）探索声音闭环神经调控技术在心衰合并失眠者外周 ANS 功能调节中的作用；3）阐明睡眠时间过短而非过长与心血管疾病之间存在因果关联；4）明确长链非编码 RNA-CHAST 是心血管疾病—急性心肌梗死心肌收缩功能的独立预测指标；5）探索开发心衰合并失眠患者的非药物干预手段。研究按计划顺利完成。项目执行期间发表SCI论文8篇。研究成果为深入理解失眠参与心衰进展的机制，以及心衰合并失眠患者的新型非药物干预手段开发提供重要的科学依据。