补阳还五汤对慢性不可预知性温和应激抑郁模型小鼠行为及脑海马CA3区病理形态学影响

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(P0.05,P0.01);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(P0.01)。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(P0.05,P0.01);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(P0.01)。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。

Effect of Buyang Huanwutang on Behavior and Pathological Morphology in Hippocampus CA3 Area in Mice Model of CUMS Depression

Objective: To investigate the neuroprotective effects and antidepressant mechanism of Buyang Huanwutang. Method: The Kunming mice were randomly divided into normal group, model group, fluoxetine group (3.0 mg·kg^-1) and Buyang Huanwu Tang low dose, middle dose and high dose groups (9.0, 18.0, 27.0 g·kg^-1, ig), n=10 in each group. The drugs were administered by ig 1 h before daily stress, and normal saline with the same volume was given in other groups, for a total of 21 d. The mice models of depression were established by chronic unpredictable mild stress (CUMS); the depression-like behavior of the mice were observed by body weight measurement (BWM), open field test (OFT) and tail suspension test (TST). The morphological changes of neurons in hippocampas CA3 area were observed by Nissl staining; the apoptosis of hippocampal neurons was observed by TUNEL method; and the ultrastructural changes of the hippocampus were observed by transmission electron microscope. Result: As compared with the normal group. depression-like behavior was found in model group, with decreased body weight, decreased scores of horizontal and vertical motion in OFT, and prolonged motionless time (P < 0.05, P < 0.01); changes of neuronal damage and early apoptosis in hippocampal CA3 area were revealed by Nissl staining and transmission electron microscope; TUNEL method showed that the number of apoptotic neurons in hippocampal CA3 area was increased (P<0.01). As compared with the model group, depression-like behavior was improved in Fluoxetine group and Buyang Huanwutang groups, with increased body weight, increased scores of horizontal and vertical motion in OFT, and less motionless time (P < 0.05, P < 0.01); neuronal damage and early apoptosis in hippocampal CA3 area were reduced in Nissl staining and transmission electron microscope; TUNEL method showed that the number of apoptotic neurons in hippocampal CA3 area was decreased (P<0.01). Conclusion: Buyang Huanwutang could improve the depression-like behavior in mice by reducing neuronal damage in hippocampus CA3 area and inhibiting the neuronal apoptosis, with neuroprotective and antidepressant effects.