目的:探讨补阳还五汤神经保护作用及抗抑郁机制。方法:清洁级昆明小鼠随机分为正常组,模型组,氟西汀组(3.0 mg·kg-1,ig),补阳还五汤低、中、高剂量组(9.0,18.0,27.0 g·kg-1,ig),每组10只。各给药组于每日应激前1 h ig给药,其余各组给予等体积生理盐水,共计21 d。采用慢性不可预知性温和应激法(CUMS)建立小鼠抑郁症模型,采用旷场实验(OFT),悬尾实验(TST)及体重测试(BWM)观察动物抑郁样行为;采用尼氏体染色检测海马CA3区神经元形态学变化;采用透射电镜观察海马区超微结构变化;采用TUNEL法检测海马CA3区神经元凋亡情况。结果:与正常组比较,模型组小鼠出现抑郁样行为,表现为体重减少,OFT水平及垂直运动得分减少及TST不动时间延长(P<0.05,P<0.01);尼氏染色及透射电镜显示海马CA3区神经元损伤及早期凋亡变化;TUNEL法显示海马CA3区神经元凋亡数量增加(P<0.01)。与模型组比较,氟西汀组及补阳还五汤各剂量组小鼠抑郁样行为均有改善,表现为体重增加,OFT水平及垂直运动得分增加,TST不动时间减少(P<0.05,P<0.01);尼氏染色及透射电镜显示海马CA3区神经元细胞损伤减轻;TUNEL法显示海马CA3区神经元凋亡数量减少,差异有统计学意义(P<0.01)。结论:补阳还五汤可能通过减轻海马CA3区神经元损伤及抑制神经元凋亡而改善小鼠抑郁样行为,具有神经保护及抗抑郁症作用。 Objective: To explore the neuroprotective effects and the antidepressant mechanisms of Buyang Huanwu Decoction. Methods: Clean Kunming mice were randomly divided into normal group, model group, fluoxetine group (3.0 mg · kg-1, ig), Buyang Huanwu Decoction low, middle and high dose group · Kg-1, ig), 10 in each group. Each administration group was administered ig 1 h prior to daily stress, and the remaining groups were given equal volume of normal saline for a total of 21 days. The model of depressive disorder in mice was established by chronic unpredictable mild stress (CUMS) model. Depression-like behavior was observed by open field test (OFT), tail suspension test (TST) and weight test (BWM) Morphological changes of hippocampal CA3 neurons were observed. Transmission electron microscopy was used to observe ultrastructural changes in hippocampus. TUNEL method was used to detect neuronal apoptosis in hippocampal CA3 area. Results: Compared with the normal group, the depression-like behavior of mice in the model group showed weight loss, decreased OFT level and vertical movement score and prolonged TST (P <0.05, P <0.01) The changes of neuron damage and early apoptosis in CA3 area of ​​hippocampus were observed. The number of neuron apoptosis in hippocampal CA3 area was increased by TUNEL assay (P <0.01). Compared with the model group, the depression-like behavior of the fluoxetine group and the Buyang Huanwu decoction group were improved, the body weight gain, OFT level and vertical movement score increased, TST immobility time decreased (P <0.05, (P <0.01). The Nissl staining and transmission electron microscopy showed that the neurons in CA3 area of ​​the hippocampus were mitigated. The number of apoptotic neurons in hippocampal CA3 area was decreased by TUNEL assay. The difference was statistically significant (P <0.01). Conclusion: Buyang Huanwu decoction may improve the depression-like behavior of mice by reducing neuronal damage and inhibiting apoptosis of neurons in CA3 area of ​​the hippocampus, which has neuroprotective and antidepressant effects.