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炎症反射在脓毒症器官损伤发生发展中的作用研究进展
周新越
王妍
方向明
作者及单位信息
·
DOI： 10.3760/cma.j.cn501098-20241009-00592
Role of the inflammatory reflex in the development and progression of organ injury in sepsis: a review
Zhou Xinyue
Wang Yan
Fang Xiangming
Authors Info & Affiliations
Zhou Xinyue
Department of Anesthesiology, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
Wang Yan
Department of Anesthesiology, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
Fang Xiangming
Department of Anesthesiology, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
·
DOI： 10.3760/cma.j.cn501098-20241009-00592
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摘要

脓毒症是指由感染引起的机体反应异常而导致危及生命的器官功能障碍，是导致患者死亡的主要病因之一，至今仍缺乏有效的预警和治疗技术。近年来，神经与免疫系统交互作用对脓毒症发生发展的影响颇受关注，但脓毒症引发脏器损伤的具体机制及器官交互作用等问题仍不明确。炎症反射即中枢神经系统整合传入的炎症信号并对外周炎症反应产生反射性调节，是中枢神经网络调控外周免疫的重要起点。通过调控炎症反射进而改善其免疫功能紊乱将是治疗脓毒症的突破点。然而，脓毒症中炎症反射如何引起机体中枢神经系统及外周免疫系统改变，以及炎症反射如何参与脓毒症中的器官损伤仍有待探讨。为此，笔者对炎症反射在脓毒症器官损伤发生发展中的作用研究进展进行综述，以期为脓毒症治疗提供新思路。

脓毒症;神经免疫调节;下丘脑-垂体系统;炎症反射
ABSTRACT

Sepsis, a life-threatening organ dysfunction caused by an abnormal host response to infection, remains one of the leading causes of mortality in critically ill patients, but there is currently a lack of effective early warning systems and therapeutic strategies for sepsis. In recent years, the interaction between the nervous and immune systems has gained considerable attention. However, the precise mechanisms underlying sepsis-related organ damage and the complex interplay among different organs remain poorly understood. The inflammatory reflex, which involves the central nervous system integrating incoming inflammatory signals and reflexively modulating peripheral inflammatory responses, is a critical interface where the central nervous network regulates peripheral immunity. Modulating the inflammatory reflex to correct immune dysfunction may represent a promising therapeutic breakthrough for sepsis. Nevertheless, the precise mechanisms by which the inflammatory reflex induces changes in both the central nervous system and the peripheral immune system in sepsis, as well as its role in organ damage, remain to be elucidated. To this end, the authors reviewed the researches on the role of the inflammatory reflex in the development and progression of sepsis-related organ damage, aiming to provide novel insights into more effective therapeutic strategies for sepsis.

Sepsis;Neuroimmunomodulation;Hypothalamo-hypophyseal system;Inflammatory reflex
Fang Xiangming, Email: nc.defudabe.ujzgnafmx
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引用本文

周新越,王妍,方向明. 炎症反射在脓毒症器官损伤发生发展中的作用研究进展[J]. 中华创伤杂志,2025,41(03)：318-324.

DOI:10.3760/cma.j.cn501098-20241009-00592

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脓毒症是指由感染引起的机体反应异常而导致危及生命的器官功能障碍，其住院病死率高达17%~26% ［ 1 ］ 。严重创伤是诱发脓毒症的重要原因，进一步发展可能导致脓毒性休克和多器官功能障碍综合征（MODS） ［ 2 ］ 。脓毒症患者多合并1个及以上器官功能的严重损害，常见的受损器官包括肺、心、肾、脑等，且由心肺等关键脏器损伤引发的功能障碍将影响患者的长期转归。研究结果表明，40%的脓毒症或脓毒性休克患者会出现急性呼吸窘迫综合征（ARDS）；超过50%的脓毒症患者合并急性肾损伤；高达70%的脓毒症危重患者患有不同程度的脓毒症相关性脑病，55%的脓毒症患者存在血小板减少症和（或）弥散性血管内凝血，46%的脓毒症患者伴有肝功能障碍 ［ 3 ］ 。但由于脓毒症引发脏器损伤的核心机制不明、器官交互作用错综复杂等原因，围绕脓毒症器官功能保护的研究仍有大量问题需要解决 ［ 4 ］ 。神经-免疫功能紊乱是导致机体免疫炎症反应失调的重要环节，也是脓毒症发病机制之一。在严重创伤中，肾上腺皮质激素释放激素（CRH）、皮质类固醇和儿茶酚胺等对启动和维持促炎反应具有重要作用 ［ 2 ］ 。目前，脓毒症如何影响大脑进而导致器官功能障碍，以及脓毒症患者神经、内分泌和免疫系统之间的相互作用被列为脓毒症相关的基础科学问题之一 ［ 5 ］ 。研究大脑对外周关键脏器的免疫调控作用及机制，包括“大脑-心脏”“脑-肺脏”“大脑-肠道”“大脑-脾脏”等的交互调控通路，对于改善脓毒症患者的预后具有重要意义。2002年，Tracey ［ 6 ］ 首次提出炎症反射概念，即中枢神经系统整合传入的炎症信号并对外周炎症反应产生反射性调节。此概念的提出成为中枢神经网络调控外周免疫的重要起点。近年来，针对炎症反射在脓毒症脏器损伤发生中作用的研究取得一些新的进展，为脓毒症患者的临床治疗奠定了一定的基础。但是，脓毒症中炎症反射对中枢神经系统和外周免疫系统的影响，以及炎症反射如何参与脓毒症相关器官损伤的机制仍不明确。
为深入了解炎症反射在脓毒症器官损伤中的作用，笔者以“sepsis”“inflammation”“inflammatory reflex”“cholinergic anti-inflammatory pathway”“hypothalamus- pituitary-adrenal axis”“neuroimmunomodulation”作为关键词，检索Web of Science、Scopus与PubMed数据库；以“脓毒症”“炎症”“炎症反射”“胆碱能抗炎通路”“下丘脑-垂体-肾上腺轴”“神经免疫调节”作为关键词，检索万方数据知识服务平台、中华医学期刊网与中国知网数据库。检索时限为建库至2024年10月。文献纳入标准：（1）关于炎症反射在脓毒症发生发展机制中的基础研究；（2）与脓毒症治疗中炎症反射调控相关的临床试验；（3）研究类型不限；（4）文献类型为论著与综述。文献排除标准：（1）无法获取全文；（2）内容重复或相似；（3）非中文或英文。最终引用文献58篇，其中英文54篇，中文4篇。笔者对炎症反射在脓毒症器官损伤发生发展中的作用研究进展进行综述，以期为脓毒症治疗提供新思路。
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备注信息
A
方向明，Email： nc.defudabe.ujzgnafmx
B

周新越：文献检索、论文撰写及修改；王妍：论文指导及修改；方向明：论文指导及修改、经费支持

C
周新越, 王妍, 方向明. 炎症反射在脓毒症器官损伤发生发展中的作用研究进展[J]. 中华创伤杂志, 2025, 41(3): 318-324. DOI: 10.3760/cma.j.cn501098-20241009-00592.
D
所有作者声明不存在利益冲突
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国家自然科学基金 (82302410)
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