神经丝轻链在脓毒症相关性脑病中的研究进展

doi:10.3969/j.issn.1674-8115.2026.10.014

上海交通大学学报（医学版） ›› 2026, Vol. 46 ›› Issue (10): 1435-1441.doi: 10.3969/j.issn.1674-8115.2026.10.014

• 综述 • 上一篇

神经丝轻链在脓毒症相关性脑病中的研究进展

周菊芳¹, 许天祥², 王晓霞¹^,³()

^1.内蒙古医科大学内蒙古临床医学院，呼和浩特 010110
^2.内蒙古自治区人民医院腹部肿瘤外科，呼和浩特 010110
^3.内蒙古自治区人民医院重症医学科，呼和浩特 010110

收稿日期:2026-04-08 接受日期:2026-05-11 出版日期:2026-10-15 发布日期:2026-10-15
通讯作者: 王晓霞，主任医师，博士；电子信箱：xiaoxiawang_2012@163.com。
基金资助:
内蒙古医学科学院公立医院科研联合基金科技项目(2023GLLH0012);内蒙古医学科学院公立医院科研联合基金科技项目(2023GLLH0038);内蒙古自治区自然科学基金项目(2023MS08019);内蒙古自治区自然科学基金项目(2018LH08002);内蒙古自治区自然科学基金项目(2023LHMS08052);内蒙古自治区卫生健康科技计划项目(2025WSJK013);内蒙古自治区卫生健康科技计划项目(2025WSJK010);内蒙古自治区人民医院博士科研启动基金(2024BS07);内蒙古医科大学联合项目(YKD2022LH015)

Research progress in neurofilament light chain in sepsis-associated encephalopathy

Zhou Jufang¹, Xu Tianxiang², Wang Xiaoxia¹^,³()

^1.Inner Mongolia Medical University, Inner Mongolia Clinical Medical College, Hohhot 010110, China
^2.Department of Abdominal Tumor Surgery, Inner Mongolia Autonomous Region People's Hospital, Hohhot 010110, China
^3.Department of Critical Care Medicine, Inner Mongolia Autonomous Region People's Hospital, Hohhot 010110, China

Received:2026-04-08 Accepted:2026-05-11 Online:2026-10-15 Published:2026-10-15
Contact: Wang Xiaoxia, E-mail: xiaoxiawang_2012@163.com.
Supported by:
Public Hospital Research Joint Fund Science and Technology Project of Inner Mongolia Academy of Medical Sciences(2023GLLH0012);Natural Science Foundation of Inner Mongolia Autonomous Region of China(2023MS08019);Health Science and Technology Plan Project of Inner Mongolia Autonomous Region(2025WSJK013);Doctoral Research Start-up Fund of People's Hospital of Inner Mongolia Autonomous Region(2024BS07);Joint Project of Inner Mongolia Medical University(YKD2022LH015)

摘要/Abstract

摘要：

脓毒症相关性脑病（sepsis-associated encephalopathy，SAE）是脓毒症患者中最为常见且严重的神经系统并发症，在重症监护室中的发生率可高达70%。SAE不仅显著增加患者的住院死亡率，更因其导致的长期认知功能障碍，严重影响幸存者的远期生活质量，给社会和家庭带来沉重负担。然而，SAE的临床表现异质性强，常被原发疾病的严重症状所掩盖，且缺乏特异性的床旁诊断工具，导致其临床识别率远低于实际发病率。传统脑损伤标志物如S100β和神经元特异性烯醇化酶（neuron-specific enolase，NSE）因受来源特异性不足及溶血等因素干扰，在临床应用中存在明显局限；而神经影像学检查虽能发现结构性异常，但阳性率低、操作繁琐且难以实现动态监测，无法满足SAE早期识别与病情动态评估的需求。因此，探索能够客观、灵敏、动态反映脓毒症脑损伤的生物标志物，成为该领域亟待突破的关键问题。神经丝轻链（neurofilament light chain，NfL）是神经元轴突细胞骨架的核心组成蛋白，在轴突受到缺血、炎症或代谢应激等损伤时，神经丝网络崩解，NfL被迅速释放至脑脊液并可穿越血脑屏障进入外周血。近年来，以单分子阵列为代表的超灵敏检测技术的成熟，使得外周血NfL的准确定量成为可能，为其在危重症领域的应用奠定了方法学基础。现有研究表明，脓毒症急性期患者血清NfL水平显著升高，且与疾病严重程度、谵妄持续时间及不良神经功能预后密切相关，展现出良好的早期诊断与预后分层价值。同时，NfL可综合反映神经炎症、缺血缺氧、线粒体功能障碍及血脑屏障破坏等多种病理通路的累积效应，被视为SAE脑损伤的“整合标志物”。该文综述了NfL的生物学基础与检测方法学进展，重点梳理了其在SAE急性期动态变化、病理生理机制关联、与传统脑损伤标志物的比较优势以及与影像学改变相关性等方面的临床研究证据。此外，还进一步探讨了基于NfL的早期识别与风险分层策略、作为潜在干预靶点的应用前景，并对当前临床转化中面临的标准化不足、肾功能影响及成本效益等挑战进行了客观分析，以期为NfL在SAE临床管理中的规范化应用及未来研究方向提供参考。

Abstract:

Sepsis-associated encephalopathy (SAE) is the most common and severe neurological complication in patients with sepsis, with an incidence rate as high as 70% in the intensive care unit. SAE not only significantly increases in-hospital mortality but also seriously affects the long-term quality of life of survivors due to the resultant long-term cognitive dysfunction, imposing a heavy burden on society and families. However, the clinical manifestations of SAE are highly heterogeneous and are often obscured by the severe symptoms of the primary disease, and the lack of specific bedside diagnostic tools leads to a clinical recognition rate far lower than the actual incidence. Traditional brain injury biomarkers, such as S100β protein and neuron-specific enolase (NSE), have obvious limitations in clinical application due to insufficient source specificity and interference from hemolysis, among other factors. Meanwhile, neuroimaging examinations, although capable of detecting structural abnormalities, suffer from low positivity rates, cumbersome operation, and difficulty in achieving dynamic monitoring, thus failing to meet the needs for early identification and dynamic assessment of SAE. Therefore, exploring biomarkers that can objectively, sensitively, and dynamically reflect sepsis-induced brain injury has become a critical issue to be addressed in this field. Neurofilament light chain (NfL) is a core component of the neuronal axonal cytoskeleton. When axons are injured by ischemia, inflammation, or metabolic stress, the neurofilament network disintegrates, and NfL is rapidly released into the cerebrospinal fluid and can cross the blood-brain barrier to enter the peripheral blood. In recent years, the maturation of ultra-sensitive detection technologies represented by single-molecule array has made accurate quantification of peripheral blood NfL feasible, laying the methodological foundation for its application in the critical care setting. Existing studies have shown that serum NfL levels are significantly elevated in patients during the acute phase of sepsis and are closely correlated with disease severity, duration of delirium, and poor neurological outcomes, demonstrating promising value for early diagnosis and prognostic stratification. Meanwhile, NfL can comprehensively reflect the cumulative effects of multiple pathological pathways, including neuroinflammation, ischemia-hypoxia, mitochondrial dysfunction, and blood-brain barrier disruption, and is thus regarded as an "integrative biomarker" of brain injury in SAE.This review elaborates on the biological basis and methodological advances in NfL detection, with a focus on summarizing the clinical research evidence regarding its acute-phase dynamic changes in SAE, associations with pathophysiological mechanisms, comparative advantages over traditional brain injury biomarkers, and correlations with imaging alterations. Furthermore, it explores the strategies for early identification and risk stratification based on NfL, as well as its potential as an intervention target, and objectively analyzes the challenges currently facing clinical translation, including lack of standardization, the influence of renal function, and cost-effectiveness, with the aim of providing references for the standardized application of NfL in the clinical management of SAE and for future research directions.

Key words: sepsis, sepsis-associated encephalopathy, neurofilament light chain, biomarker, brain dysfunction, axonal transport

中图分类号:

R631.2

周菊芳, 许天祥, 王晓霞. 神经丝轻链在脓毒症相关性脑病中的研究进展[J]. 上海交通大学学报（医学版）, 2026, 46(10): 1435-1441.

Zhou Jufang, Xu Tianxiang, Wang Xiaoxia. Research progress in neurofilament light chain in sepsis-associated encephalopathy[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2026,(10): 1435-1441.

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神经丝轻链在脓毒症相关性脑病中的研究进展

Research progress in neurofilament light chain in sepsis-associated encephalopathy

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