复方柴金解郁片对慢性温和不可预知性应激抑郁大鼠海马突触可塑性的影响

Effects of Compound Chaijin Jieyu Tablets on Synaptic Plasticity in Hippocampus of Chronic Unpredictable Mild Stress Depressed Rats

目的观察复方柴金解郁片对慢性温和不可预知性应激抑郁大鼠海马神经元突触可塑性的影响,探讨其抗抑郁的作用机制。方法将SD大鼠随机分为空白组、模型组、文拉法辛组和复方柴金解郁片高、中、低剂量组,每组10只,除空白组外,采用慢性温和不可预知性应激结合孤养建立抑郁大鼠模型,同时灌胃相应药物,连续42 d。采用糖水消耗实验、旷场实验、强迫游泳实验进行行为学评价,HE染色观察大鼠海马组织病理变化,高尔基染色观察海马神经元树突棘变化,Western blot检测海马组织胶质细胞源性神经营养因子(GDNF)、树突棘素(Spinophilin)蛋白表达。结果与空白组比较,模型组大鼠糖水偏好度降低,总活动次数显著减少,游泳不动时间显著增加(P<0.05,P<0.01),海马神经元突触损伤,排列紊乱,树突棘数量减少或缺失,海马组织GDNF、Spinophilin蛋白表达显著降低(P<0.05,P<0.01);与模型组比较,文拉法辛组和复方柴金解郁片中、低剂量组大鼠糖水偏好度升高,总活动次数显著增加,游泳不动时间显著减少(P<0.05,P<0.01),海马神经元突触损伤减轻,树突分支和树突棘数量增加,海马组织GDNF、Spinophilin蛋白表达显著升高(P<0.05,P<0.01)。结论复方柴金解郁片可改善慢性温和不可预知性应激大鼠抑郁样行为,其机制可能与上调海马组织GDNF、Spinophilin蛋白表达,调控海马神经元突触可塑性有关。

Objective To observe the effects of Compound Chaijin Jieyu Tablets on the synaptic plasticity of hippocampus in chronic unpredictable mild stress depressed rats;To discuss its mechanism of anti-depression.Methods SD rats were randomly divided into blank group,model group,venlafaxine group,Compound Chaijin Jieyu Tablets high-,medium-and low-dosage groups,with 10 rats in each group.Except for the blank group,chronic unpredictable mild stress combined with solitary rearing was used to establish the model of depression rats,and at the same time,gavage with corresponding medicine was performed for consecutive 42 days.Sugar water consumption test,open-field test and forced swimming test were used for behavioral evaluation.Pathological changes of hippocampal tissue was observed by HE staining,and changes of dendritic spines of hippocampal neurons were observed by Golgi staining.Western blot was used to detect the expressions of glial cell-derived neurotrophic factor(GDNF)and Spinophilin protein in hippocampus.Results Compared with the blank group,sugar water preference and total activity times of the rats in model group significantly decreased,immotility time increased(P<0.05,P<0.01),synaptic damage and disorder of hippocampal neurons,and the number of dendritic spines significantly decreased or lost,the expressions of GDNF and Spinophilin protein in hippocampal tissue significantly decreased(P<0.05,P<0.01).Compared with the model group,sugar water preference of the rats in venlafaxine group,Compound Chaijin Jieyu Tablets medium-and low-dosage groups significantly increased,total activity times significantly increased,immotility time significantly decreased(P<0.05,P<0.01),synaptic damage of hippocampal neurons was reduced,the number of dendritic arborizations and dendritic spines increased,and the expressions of GDNF and Spinophilin protein in hippocampal tissue significantly increased(P<0.05,P<0.01).Conclusion Compound Chaijin Jieyu Tablets can improve depression-like behavior in chronic unpredictable mild stress rats,and the mechanism may be related to the up-regulation of GDNF and Spinophilin protein expression in hippocampal tissue and the regulation of synaptic plasticity in hippocampal neurons.