开心散对APP/PS1转基因小鼠在体LTP和PSD-95表达的影响

摘要

目的 考察开心散(远志、人参、茯苓、石菖蒲)对APP/PS1转基因小鼠海马在体长时程增强(LTP)、海马CA1区和大脑皮层突触后致密蛋白-95 (PSD-95)的表达的影响.方法 32只APP/PS1雄性小鼠(3月龄)随机均分为模型组、多奈哌齐[0.75 mg/(kg-d)]组、开心散[1.5、3 g/(kg·d)]组,另设C57/BL6小鼠为对照组,连续给药3个月.记录海马区穿通纤维通路(perforant pathway,PP)至齿状回(dentate gyrus,DG)的在体LTP,免疫组化法观察小鼠海马CA1区、大脑皮层PSD-95的表达.结果 与对照组相比,模型组小鼠场兴奋性突触后电位(fEP-SP)斜率明显下降,海马CA1区、大脑皮层中PSD-95阳性细胞的平均光密度明显减少;而多奈哌齐、开心散可明显提高模型组小鼠fEPSP斜率.多奈哌齐能增加海马CA1区PSD-95阳性细胞的平均光密度,开心散[1.5 g/(kg·d)]可以增加海马CA1区、大脑皮层PSD-95阳性细胞的平均光密度,开心散[3 g/(kg,d)]能增加大脑皮层PSD-95阳性细胞的平均光密度.结论 开心散能促进APP/PS1转基因小鼠LTP形成,增强突触可塑性,可能与调节PSD-95蛋白表达有关.%AIM To explore the effects of Kaixin Powder (Polygalae Radix,Ginseng Radix et Rhizoma,Poria and Acori tatarinowii Rhizoma) on hippocampal long-term potentiation (LTP) in vivo in APP/PS1 transgenic mice and expression of PSD-95 in hippocampus CA1 area and cerebral cortex.METHODS Thirty-two 3-monthold male APP/PS1 mice were randomly divided into model group,Donepezil [0.75 mg/(kg · d)] group,Kaixin Powder [1.5,3 g/(kg · d)] groups.C57/BL6 mice were used as the control group.Kaixin Powder and Donepezil were administered to the APP/PS1 mice for three months,respectively.Afterwards,the LTP in vivo was recorded in a perforant pathway-dentate gyrus in the hippocampus.Immunohistochemical method was used for measuring the expression of PSD-95 in hippocampus CA1 area and cerebral cortex.RESULTS The fEPSPs slopes were significantly decreased in the model group as compared with the control group.Kaixin Powder or Donepezil treatment significantly enhanced the fEPSPs slopes in the model group.The average optical density of PSD-95 positive cells in hippocampus CA1 area and cerebral cortex was obviously decreased in the model group.Donepezil increased the average optical density of PSD-95 positive cells in hippocampus CA1 area.Kaixin Powder [1.5 g/(kg · d)] increased the average optical density of PSD-95 positive cells in hippocampus CA1 area and cerebral cortex.Kaixin Powder [3 g/(kg · d)] increased the average optical density of PSD-95 positive cells in cerebral cortex.CONCLUSION Kaixin Powder can promote the LTP formation in APP/PS1 transgenic mice and enhance synaptic plasticity,which may be related to the regulation of protein expression of PSD-95.