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电针通过调节氧化应激介导的NLRP3/ASC/半胱天冬酶-1通路抑制小胶质细胞激活:减轻炎症性肠病中的神经炎症和抑郁

Electroacupuncture Regulates Oxidative Stress-Mediated NLRP3/ASC/Caspase-1 Pathway to Inhibit Microglial Activation: Alleviating Neuroinflammation and Depression in IBD.

作者信息

Li Zuqiang, Cao Sihui, Yang Jingjing, Chen Lin, Jia Lv, Lu Penghui, Liu Jin, Liu Mi, Liu Qiong

机构信息

School of Acupuncture-Moxibustion, Tuina and Rehabilitation, Hunan University of Chinese Medicine, Changsha, Hunan, 410208, People's Republic of China.

Department of Psychiatry, National Clinical Research Center for Mental Disorders, and National Center for Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha, Hunan, 410011, People's Republic of China.

出版信息

J Inflamm Res. 2025 Aug 29;18:11935-11950. doi: 10.2147/JIR.S534219. eCollection 2025.

Abstract

PURPOSE

This study aims to investigate the efficacy of electroacupuncture in treating inflammatory bowel disease (IBD) accompanied by depressive symptoms. The potential mechanisms of electroacupuncture are also investigated, particularly in terms of its modulation of oxidative stress and NLRP3 inflammasomes to influence microglial activation and neuroinflammation, thereby alleviating depressive symptoms.

MATERIAL AND METHODS

The inflammatory bowel disease model in mice was induced by dextran sulfate sodium (DSS), and the mice were randomly assigned to the CON group, DSS group, DSS+EA group, and DSS+ MCC950 group. The assessment of depressive-like behavior in mice involved behavioral tests, while the detection of oxidative stress in the PFC, NLRP3 inflammasomes, central inflammation expression, and microglial activation were conducted using enzyme-linked immunosorbent assay (ELISA), Western blot, immunofluorescence, and biochemical kits.

RESULTS

Mice in the DSS group exhibited significant depressive-like behavior, which was effectively alleviated by electroacupuncture intervention. The intervention also reduced the expression of inflammatory factors and microglial activation in the medial prefrontal cortex (PFC) region. Electroacupuncture effectively attenuated oxidative stress, suppressed the recruitment of NLRP3 inflammasomes, and mitigated central nervous system inflammation, with effects similar to those of the NLRP3 inhibitor MCC950.

CONCLUSION

Electroacupuncture significantly alleviated depressive symptoms in IBD mice by inhibiting oxidative stress and microglial activation in the PFC region, thereby ameliorating the neuroinflammatory environment. The findings can provide new theoretical and scientific support for the clinical application of electroacupuncture in treating depressive symptoms associated with IBD.

摘要

目的

本研究旨在探讨电针治疗伴有抑郁症状的炎症性肠病(IBD)的疗效。同时研究电针的潜在机制,特别是其对氧化应激和NLRP3炎性小体的调节作用,以影响小胶质细胞活化和神经炎症,从而减轻抑郁症状。

材料与方法

采用葡聚糖硫酸钠(DSS)诱导小鼠炎症性肠病模型,并将小鼠随机分为对照组、DSS组、DSS+电针组和DSS+MCC950组。通过行为测试评估小鼠的抑郁样行为,使用酶联免疫吸附测定(ELISA)、蛋白质免疫印迹法、免疫荧光法和生化试剂盒检测前额叶皮质(PFC)中的氧化应激、NLRP3炎性小体、中枢炎症表达和小胶质细胞活化情况。

结果

DSS组小鼠表现出明显的抑郁样行为,电针干预可有效缓解该行为。该干预还降低了内侧前额叶皮质(PFC)区域炎症因子的表达和小胶质细胞活化。电针有效减轻了氧化应激,抑制了NLRP3炎性小体的募集,并减轻了中枢神经系统炎症,其效果与NLRP3抑制剂MCC950相似。

结论

电针通过抑制PFC区域的氧化应激和小胶质细胞活化,显著减轻了IBD小鼠的抑郁症状,从而改善了神经炎症环境。这些发现可为电针在治疗与IBD相关的抑郁症状中的临床应用提供新的理论和科学支持。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5bbb/12406034/b04a10a53832/JIR-18-11935-g0001.jpg

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