帕金森病的心率变异性：从病理机制到临床 转化

Heart Rate Variability in Parkinson’s Disease: From Pathological Mechanisms to Clinical Translation

摘要: 帕金森病(PD)是一种以黑质多巴胺能神经元退行性变及α-突触核蛋白异常聚集为主要特征的神经系统变性疾病。既往研究多聚焦于运动症状，而自主神经功能障碍等非运动症状的早期出现及其对预后的影响日益受到重视。心率变异性(HRV)作为无创评估自主神经系统功能的关键生物标志物，可反映交感神经与副交感神经对心脏节律的动态调控，其异常改变与PD的病理进程高度相关。α-突触核蛋白在迷走神经背核、蓝斑核、交感神经节等中枢及外周自主神经结构中的异常沉积与传播，通过干扰神经递质释放、抑制Wnt/β-连环蛋白通路、诱导线粒体功能障碍及神经炎症等机制，导致自主神经调控失衡，进而使HRV的时域、频域及非线性指标显著降低。临床证据表明，PD患者的HRV下降具有普遍性，且与疾病分期、病程进展及前驱期(如特发性快速眼动睡眠行为障碍)密切相关，同时受年龄、药物及康复干预等因素影响。HRV在PD早期筛查、鉴别诊断、预后评估及治疗反应监测中具有潜在应用价值，可作为多模态生物标志物的重要组成部分。然而，当前HRV检测与分析存在标准化方案不统一、混杂因素较多、特异性有限等问题，限制了其临床转化。未来需依托多中心前瞻性研究、可穿戴设备与人工智能技术，建立标准化评估流程，结合病理、基因与影像等多维度数据，推动HRV成为PD精准诊疗与长期监测的实用工具，为改善患者自主神经症状及生活质量提供新策略。

Abstract: Parkinson’s disease (PD) is a neurodegenerative disorder primarily characterized by the degeneration of dopaminergic neurons in the substantia nigra and the abnormal aggregation of α-synuclein. Previous research has predominantly focused on motor symptoms, whereas increasing attention has been paid to the early emergence of non-motor symptoms, such as autonomic dysfunction, and their impact on prognosis. Heart rate variability (HRV), a key biomarker for the noninvasive assessment of autonomic nervous system function, reflects the dynamic regulation of cardiac rhythm by the sympathetic and parasympathetic nerves, with its abnormal changes being highly correlated with the pathological progression of PD. The abnormal deposition and propagation of α-synuclein in central and peripheral autonomic nerve structures, including the dorsal motor nucleus of the vagus, locus coeruleus, and sympathetic ganglia, disrupt autonomic regulation by interfering with neurotransmitter release, inhibiting the Wnt/β-catenin pathway, inducing mitochondrial dysfunction, and triggering neuroinflammation, thereby significantly reducing the time-domain, frequency-domain, and nonlinear indices of HRV. Clinical evidence indicates that HRV reduction is prevalent in PD patients and is closely associated with disease stage, progression, and prodromal conditions (e.g., idiopathic rapid eye movement sleep behavior disorder), while also being influenced by factors such as age, medication, and rehabilitation interventions. HRV holds potential application value in the early screening, differential diagnosis, prognosis evaluation, and treatment response monitoring of PD, serving as a crucial component of multimodal biomarkers. However, current HRV detection and analysis face challenges such as inconsistent standardization protocols, numerous confounding factors, and limited specificity, which hinder its clinical translation. Future efforts should leverage multicenter prospective studies, wearable devices, and artificial intelligence technologies to establish standardized assessment procedures and integrate multidimensional data, including pathology, genetics, and imaging, to facilitate the practical application of HRV as a tool for precise diagnosis and long-term monitoring of PD, thereby offering novel strategies for improving patients’ autonomic symptoms and quality of life.