近年来研究表明，肠道菌群与嘌呤能受体P2X7（P2X purinoceptor 7 receptor，P2X7R）/NOD样受体热蛋白结构域3（NOD like receptor family pyrin domain containing 3，NLRP3）信号通路在抑郁症的神经炎症和代谢调控中发挥重要作用。研究聚焦于肠道菌群与P2X7R/NLRP3信号通路的相互作用，系统阐释了其在抑郁症神经炎症及代谢调控中的潜在作用。其中包括肠道菌群通过其代谢产物调节机体的免疫和代谢功能，从而抑制P2X7R/NLRP3信号通路异常激活，改善抑郁样行为；反之，该信号通路的异常激活又会加剧肠道菌群失调，形成“菌群-炎症-代谢”恶性循环。基于此，针对“肠道菌群-P2X7R/ NLRP3”信号轴的治疗策略展现出了显著的潜力，其中以中药单体（如大麻二酚、小檗碱、红景天苷）、中药复方（如黄连解毒汤、吴茱萸汤）为代表的治疗策略，可通过该信号轴的互作机制，有效阻断神经炎症并改善能量代谢。因此，创新性地构建了“肠道菌群-P2X7R/NLRP3”信号轴在抑郁症中的双向调控理论框架，并基于此总结了针对性的治疗策略，为抑郁症的治疗提供重要的理论基础。

Recent studies have shown that the gut microbiota and P2X purinoceptor 7 receptor (P2X7R)/NOD-like receptor family pyrin domain-containing protein 3 (NLRP3) signaling pathway play critical roles in neuroinflammation and metabolic regulation in depression. This research focuses on the interaction between the gut microbiota and P2X7R/NLRP3 signaling pathway, systematically elucidating its potential role in depression-related neuroinflammation and metabolic regulation. Key findings include: the gut microbiota regulates immune and metabolic functions through their metabolites, thereby suppressing abnormal activation of P2X7R/NLRP3 signaling pathway and alleviating depressive-like behaviors, conversely, aberrant activation of this pathway exacerbates gut microbiota dysbiosis, thereby forming a vicious cycle of “microbiota-inflammation-metabolism”. Based on these findings, targeting “gut microbiota-P2X7R/NLRP3” axis has emerged as a promising therapeutic strategy. Notably, herbal medicine interventions—including bioactive monomers (e.g., cannabidiol, berberine, salidroside) and classical formulations (e.g., Huanglian Jiedu Decoction, Wuzhuyu Decoction)—demonstrate therapeutic efficacy through this signaling axis by mitigating neuroinflammatory cascades and restoring energy metabolism. This work innovatively establishes a bidirectional regulatory framework for “gut microbiota-P2X7R/NLRP3” axis in depression and proposes mechanism-guided therapeutic approaches, providing a critical theoretical foundation for advancing depression treatment strategies.

R285

国家自然科学基金资助项目（82174357）；湖南省中医药管理局科研课题（B2023141）；湖南省科药联合基金资助项目（2023JJ60476，2025JJ80123）；湖南省科校联合基金资助项目（2025JJ90061）；湖南省卫健委一般项目（w20243097）；湖南省教育厅优青项目（23B0360，24B0342）；长沙市自然科学基金资助项目（kq2502215）；中药粉体与创新药物研究省部共建国家重点实验室培育基地开放基金（24PTKF1013）；湖南省自然科学基金创新研究群体项目（2024JJ1007）