Song Xingke, Zhu Haohan, Chen Zijie, Wang Yifei, Zhang Jinling, Wang Yu, Rong Peijing, Wang Junying
Institute of Acupuncture and Moxibustion, China Academy of Chinese Medical Sciences, Beijing, China.
Institute Of Basic Research In Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing, China.
Front Immunol. 2025 May 16;16:1536056. doi: 10.3389/fimmu.2025.1536056. eCollection 2025.
OBJECTIVES: This study aims to investigate the mechanisms of transcutaneous auricular vagus nerve stimulation (taVNS) in a lipopolysaccharide (LPS)-induced acute inflammatory depression model in rats, focusing on the regulation of peripheral pro- and anti-inflammatory cytokines and the effects on the NF-κB signaling pathway in the prefrontal cortex. METHODS: A depressive-like behavior model was established via intraperitoneal injection of LPS, and rats were randomly assigned to a normal group, a model group, and a taVNS intervention group. Behavioral assessments included the sucrose preference test (SPT), open field test (OFT), and elevated plus maze test (EPM) to evaluate depressive-like behaviors. Bio-Plex suspension array technology was used to detect inflammatory cytokine levels in serum, and Western blotting was performed to analyze the expression of NF-κB signaling pathway-related proteins in the prefrontal cortex. RESULTS: Behavioral tests demonstrated that LPS-induced rats exhibited significant depressive-like behaviors, including reduced sucrose preference, decreased activity levels in the open field, and restricted exploratory behavior in the elevated plus maze. taVNS intervention significantly alleviated these depressive-like behaviors. Serum analysis revealed that pro-inflammatory cytokines (e.g., IL-1β, TNF-α, MCP-1, IL-18, MIP-1α, and MIP-3α) were markedly elevated, while anti-inflammatory cytokines IL-4 and IL-10 were significantly reduced in the model group. taVNS intervention reversed these changes. Western blot analysis showed significant activation of the NF-κB signaling pathway in the model group, characterized by increased p-P65/P65 and p-IκB/IκB ratios and elevated TNF-α expression. taVNS intervention suppressed excessive activation of the NF-κB pathway by reducing p-P65 and TNF-α levels and stabilizing IκB expression. CONCLUSIONS: This study demonstrates that taVNS significantly improves LPS-induced depressive-like behaviors by modulating peripheral pro- and anti-inflammatory cytokine levels and inhibiting the activation of the NF-κB signaling pathway in the prefrontal cortex. These findings highlight the critical role of taVNS in the regulation of the peripheral-central inflammation network and provide theoretical support for the development of taVNS-based non-invasive neuromodulation therapies.
目的：本研究旨在探讨经皮耳迷走神经刺激（taVNS）在脂多糖（LPS）诱导的大鼠急性炎症性抑郁模型中的作用机制，重点关注外周促炎和抗炎细胞因子的调节以及对前额叶皮质中NF-κB信号通路的影响。 方法：通过腹腔注射LPS建立抑郁样行为模型，将大鼠随机分为正常组、模型组和taVNS干预组。行为学评估包括蔗糖偏好试验（SPT）、旷场试验（OFT）和高架十字迷宫试验（EPM），以评估抑郁样行为。采用生物悬浮芯片技术检测血清中炎症细胞因子水平，并进行蛋白质免疫印迹分析前额叶皮质中NF-κB信号通路相关蛋白的表达。 结果：行为学测试表明，LPS诱导的大鼠表现出明显的抑郁样行为，包括蔗糖偏好降低、旷场活动水平下降以及高架十字迷宫中的探索行为受限。taVNS干预显著减轻了这些抑郁样行为。血清分析显示，模型组促炎细胞因子（如IL-1β、TNF-α、MCP-1、IL-18、MIP-1α和MIP-3α）显著升高，而抗炎细胞因子IL-4和IL-10显著降低。taVNS干预逆转了这些变化。蛋白质免疫印迹分析显示，模型组中NF-κB信号通路显著激活，表现为p-P65/P65和p-IκB/IκB比值增加以及TNF-α表达升高。taVNS干预通过降低p-P65和TNF-α水平并稳定IκB表达来抑制NF-κB通路的过度激活。 结论：本研究表明，taVNS通过调节外周促炎和抗炎细胞因子水平以及抑制前额叶皮质中NF-κB信号通路的激活，显著改善LPS诱导的抑郁样行为。这些发现突出了taVNS在调节外周-中枢炎症网络中的关键作用，并为基于taVNS的非侵入性神经调节疗法的开发提供了理论支持。
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