摘要
术后认知功能障碍(POCD)的核心机制为围手术期神经炎性反应的级联激活。手术创伤释放损伤相关分子模式(DAMPs),通过激活外周TLR4/NF-κB通路,促进促炎因子(IL-1β、TNF-α)释放。这些因子通过破坏血脑屏障完整性或经迷走神经传入中枢,驱动小胶质细胞M1极化及星形胶质细胞活化。活化的胶质细胞释放活性氧(ROS)和炎性介质,直接损伤神经元线粒体功能,抑制突触可塑性,并诱导谷氨酸兴奋性毒性。围手术期协同因素(如麻醉药物、疼痛、昼夜节律紊乱)进一步放大炎性反应:激活NLRP3炎性小体、抑制时钟基因(Bmal1/Per2)表达,以及肠道菌群失调介导的脂多糖(LPS)-TLR4信号增强,形成“外周-中枢”恶性循环。胶质细胞极化失衡(M1/M2表型转换障碍)及炎性因子与神经元的交互作用(如HMGB1介导的NMDA受体过度激活)是导致认知损害的关键环节。深入解析神经炎性反应的动态调控网络,将为POCD的精准干预提供理论依据。
The core mechanism of postoperative cognitive dysfunction(POCD)involves a cascade activation of perioperative neuroinflammatory responses.Surgical trauma releases damage-associated molecular patterns(DAMPs),which activate the peripheral TLR4/NF-κB pathway,leading to the release of pro-inflammatory cytokines(IL-1β,TNF-α).These cytokines disrupt blood-brain barrier integrity or transmit signals via the vagus nerve to the central nervous system,driving the polarization of microglia toward the pro-inflammatory M1 phenotype and activating astrocytes.Activated glial cells release reactive oxygen species(ROS)and inflammatory mediators,which directly impair neuronal mitochondrial function,suppress synaptic plasticity,and induce glutamate excitotoxicity.Perioperative synergistic factors(e.g.,anesthetics,postoperative pain,circadian rhythm disruption)further amplify neuroinflammation by activating the NLRP3 inflammasome,suppressing clock gene(Bmal1/Per2)expression,and enhancing gut microbiota dysbiosis-mediated lipopolysaccharide(LPS)-TLR4 signaling,thereby forming a“peripheral-central”inflammatory vicious cycle.Imbalanced glial polarization(dysfunctional M1/M2 phenotype switching)and interactions between inflammatory factors and neurons(e.g.,HMGB1-mediated overactivation of NMDA receptors)collectively contribute to synaptic dysfunction and cognitive decline.Elucidating the dynamic regulatory network of neuroinflammation is pivotal l for developing precise interventions for POCD.
作者
尹静
陈春玲
YIN Jing;CHEN Chunling(Department of Anesthesiology,the First Affiliated Hospital of Xinjiang Medical University,Urumqi 830011,China)
出处
《基础医学与临床》
2026年第4期602-606,共5页
Basic and Clinical Medicine
基金
新疆维吾尔自治区重点实验室开放课题(2022D04020)。
