“调神醒脑”针法干预抑郁状态下NLRP3炎症小体信号通路的机制研究

Depression is a common affective disorder which seriously harms human health in modern society. As the core of the inflammatory response, the activation of Nod like receptor 3 (NLRP3) inflammasome has become a new hotspot in the pathogenesis of depression. Acupuncture treatment of depression not only improves the mental symptoms, but also alleviates the physical symptoms, which indicates the advantages of overall regulation. However, its mechasims remain unclear. We previously found that acupuncture could reduce pro-inflammatory cytokines in the hippocampus and prefrontal cortex in a chronic stress rat model of depression, and reduced inflammation in the brain. Therefore, we intend to further our study and put forward the following hypothesis based on previous work: “The antidepressant effect of acupuncture may be mediated by affecting the ROS/TXNIP/NLRP3 pathway induced by chronic stress, thereby attenuating inflammatory response and pyroptosis mediated by NLRP3 inflammasome activation, which lead to the protection of the brain and the antidepressant effect. ” In this study, by using techniques such as behavioral tests, molecular biology, double immunofluorescence method, electron microscopy, and intracerebroventricular injection, we will investigate the effect of acupuncture of NLRP3 inflammasome signal pathway in depression. We try to discover the scientific meaning of acupuncture of refreshing brain and regulating mind for the treatment of depression, and provide scientific basis for clinical application.

抑郁症是危害现代社会人类健康的常见情感性精神障碍。Nod 样受体蛋白 3（NLRP3）炎症小体的活化作为炎症反应的核心参与抑郁症发病过程，正成为抑郁症研究的新热点。针刺治疗抑郁症既改善精神症状，又缓解躯体症状，具有整体调节的优势，但其机制尚不明确。我们前期研究表明，针刺可以降低抑郁大鼠海马、前额叶皮层促炎细胞因子表达，缓解脑内炎症反应。本课题是前期工作的延续和深入，我们提出工作假说：“针刺可能通过调控慢性应激激活的ROS/TXNIP/NLRP3信号通路，缓解NLRP3炎症小体活化及继发的脑内炎症反应和细胞焦亡，发挥脑保护作用，产生抗抑郁效应”。本研究采用行为学、分子生物学、免疫荧光双标法、电镜、侧脑室注射等技术方法，观察针刺对抑郁状态下NLRP3炎症小体信号通路的作用机制，阐明“调神醒脑”针法治疗抑郁症的新途径，为临床应用提供科学依据。