目的 探究逍遥散防治乳腺癌性抑郁的作用机制。方法 C57BL/6小鼠通过原位注射E0771乳腺癌细胞建立荷瘤小鼠模型，给予逍遥散干预28 d，通过行为学实验检测小鼠的抑郁程度，运用蛋白组学寻找潜在的病理机制，通过病理学分析和炎症因子检测明确乳腺癌性抑郁产生的病因以及逍遥散防治乳腺癌性抑郁的作用机制。使用脂多糖处理BV2小胶质细胞构建体外模型，并使用逍遥散含药血清进行干预，验证动物实验结果。结果 与模型组比较，逍遥散显著改善乳腺癌小鼠旷场实验和高架十字迷宫实验的抑郁样行为（P＜0.01、0.001）；蛋白组学结果显示，逍遥散缓解乳腺癌性抑郁与改善神经突触功能和炎症浸润等过程有关；炎症因子检测和病理学分析结果表明，逍遥散能减轻乳腺癌所致的海马组织炎症因子浸润（P＜0.01、0.001），抑制iNOS的表达并促进CD206表达，改善神经损伤。体外实验结果显示，逍遥散含药血清能抑制脂多糖诱导的BV2细胞炎症因子分泌（P＜0.01、0.001）。结论 逍遥散通过促进M2型胶质细胞极化，减轻海马神经元炎症浸润性损伤，缓解乳腺癌所致的抑郁症状。

Objective To explore the mechanism of Xiaoyao San (逍遥散) in preventing and treating depression caused by breast cancer. Methods C57BL/6 mice were injected with E0771 breast cancer cells in situ to establish a tumor bearing mouse model. Xiaoyao San was given to intervene for 28 d, the degree of depression in mice was detected through behavioral experiments, and the potential pathological mechanism was found through proteomics. The etiology of depression caused by breast cancer and the mechanism of Xiaoyao San in preventing and treating depression caused by breast cancer were identified through pathological analysis and inflammatory factor detection. An in vitro model of BV2 microglia cells treated with lipopolysaccharide was constructed, and intervened with Xiaoyao San drug containing serum to verify the results of animal experiments. Results Compared with model group, Xiaoyao San significantly improved the depressive behavior of breast cancer mice in open field test and elevated cross maze test (P < 0.01, 0.001); The proteomic results showed that the relief of breast cancer-related depression by Xiaoyao San was related to the improvement of synaptic function and inflammatory infiltration; The results of inflammatory factor detection and pathological analysis showed that Xiaoyao San could reduce the inflammatory factor infiltration in hippocampus caused by breast cancer (P < 0.01, 0.001), inhibit the expression of iNOS and promote the expression of CD206, and improve nerve injury. The in vitro experimental results showed that the serum containing Xiaoyao San could inhibit the secretion of inflammatory factors in BV2 cells induced by lipopolysaccharide (P < 0.01, 0.001). Conclusion Xiaoyao San could promote the polarization of M2 type glial cells, alleviate the inflammatory and invasive damage of hippocampal neurons, and alleviate the depressive symptoms caused by breast cancer.

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国家自然科学基金资助项目（82274513）；国家自然科学基金资助项目（82305234）；国家自然科学基金资助项目（82474504）；广东省自然科学基金资助项目（2023A1515011115）；中医药广东省实验室（横琴实验室）科技研发培植项目（HQL2024PZ023）；广州市科技计划项目（SL2023A03J01120，SL2023A04J00228）；广东省中医院中医药科技专项科研项目（YN2022QN32）；广东省中医证候临床研究重点实验室项目（YN2023ZH10）；中医湿证国家重点实验室自主项目（QZ2023ZZ13）