甘麦大枣汤对抑郁模型大鼠海马神经元突触结构及结构蛋白表达的影响*

目的: 观察甘麦大枣汤对抑郁模型大鼠行为学及单胺递质的影响,并从突触结构及结构蛋白MAP-2与GAP-43表达改变探讨其潜在作用机制。方法: 60只SD大鼠随机分为5组:正常对照组、模型组、氟西汀组(10.8 mg/kg)、甘麦大枣汤高、低剂量组(9.72、4.86 g/kg),每组12只。除对照组外,其余各组大鼠均采用慢性不可预见性温和应激(CUMS)建立抑郁模型,并于造模同时给药组灌胃给药,连续21 d。采用糖水消耗实验和旷场测试评价大鼠抑郁样行为,ELISA法检测海马单胺递质5-HT、NE含量,Golgi染色观察神经元突触损伤情况,免疫组化法和Western blot法检测海马突触结构蛋白MAP-2和GAP-43的表达。结果: 与对照组比较,抑郁模型大鼠糖水偏好度及自主活动评分均显著下降(P＜0.01),海马5-HT、NE含量显著下降(P＜0.01),树突棘缺失明显,同时MAP-2和GAP-43表达均显著下调(P＜0.01);甘麦大枣汤干预后,模型大鼠抑郁样行为明显缓解(P＜0.01),5-HT、NE含量显著升高(P＜0.05),树突棘密度、长度及分枝增加,MAP-2和GAP-43表达显著回升(P＜0.01)。结论: 甘麦大枣汤能改善抑郁模型大鼠的抑郁样行为,升高海马单胺递质含量,其作用可能与上调突触结构蛋白、缓解神经元突触损伤有关。

Effects of Ganmai Dazao Tang on synaptic structure of hippocampal neurons in depression model rats

Objective: To investigate the effects of Ganmai Dazao Tang on behavior and monoamine neurotransmitters in rats with depression, and to explore its potential mechanism from synaptic structure. Methods: Sixty SD rats were randomly divided into 5 groups: normal control group, model group, fluoxetine group (10.8 mg/kg), Ganmai Dazao Tang high and low dose group (9.72, 4.86 g/kg), 12 rats in each group. Except the control group, the rats in the other groups were all chronically unpredictable mild stress (CUMS) to establish a depression model, and were treated by intragastric administration for 21 days. The depression-like behaviors of rats were evaluated by sucrose consumption test and open field test. The contents of serotonin (5-HT) and norepinephrine (NE) in hippocampus were detected by ELISA. The synaptic damage of neurons was observed by Golgi staining. The synaptic structure protein expression levels of MAP-2 and GAP-43 of hippocampus were detected by Immunohistochemistry and Western blot. Results: Compared with control group, the sucrose preference and autonomic activity scores of the depression model rats were decreased significantly (P＜0.01), the levels of 5-HT and NE in hippocampus were decreased significantly (P＜0.01), and the dendritic spines were absent, and the expressions of MAP-2 and GAP-43 were down-regulated significantly (P＜0.01). After treated with Ganmai Dazao Tang, the depression-like behavior of the model rats was significantly relieved (P＜0.01), and the levels of 5-HT and NE were increased (P＜ 0.05). Dendritic spine density, length and branching were increased, the expressions of MAP-2 and GAP-43 were increased (P＜ 0.01). Conclusion: Ganmai Dazao Tang can improve the depression-like behavior of depression model rats and increase the monoamine neurotransmitter content in hippocampus, which may be related to up-regulation of synaptic structural proteins and relief of synaptic damage in neurons.