补阳还五汤对血管性痴呆大鼠学习记忆功能及海马组织ERK2与CaMKⅡβ蛋白表达的影响

Effect of Buyanghuanwu decoction on the expression of ERK2 and CaMK Ⅱβ in hippocampus tissue and on ability of learning and memory in vascular dementia rats

目的:观察补阳还五汤对血管性痴呆(VD)大鼠学习记忆功能及其相关蛋白ERK2与CaMKⅡβ表达的影响。方法:采用Pulsinelli’s4血管阻断法制备VD动物模型,设假手术组、模型组、补阳还五汤组、尼莫地平组,在术后第7d、14d、28d,利用水迷宫试验对各组大鼠进行行为学检测;术后第30d,采用HE染色方法观察海马CA1区形态学变化并进行神经元计数;采用Westernblotting方法观察大鼠CA1区海马组织ERK2与CaMKⅡβ蛋白表达变化。结果:与假手术组比较,模型组大鼠学习与记忆成绩明显下降(P<0.05);海马CA1区神经元排列紊乱,出现凝固性坏死,细胞脱失明显;ERK2与CaMKⅡβ蛋白表达显著降低(P<0.05)。与模型组比较,补阳还五汤组、尼莫地平组大鼠学习和记忆成绩均明显好转(P<0.05);海马CA1区神经元排列整齐,细胞形态正常,脱失不明显,接近假手术组;ERK2与CaMKⅡβ蛋白表达显著增多(P<0.05)。结论:补阳还五汤可能通过促进VD大鼠ERK2蛋白和CaMKⅡβ蛋白的表达,从而促进突触构建和学习记忆功能的恢复。

AIM： To investigate the effect of Buyanghuanwu decoction,a Chinese medicine,on the ability of learning and memory in the rats with vascular dementia （ VD） and on the protein expression of extracellular signal-regulated kinase 2（ ERK2） and calcium/calmodulin-dependent protein kinase Ⅱβ（ CaMKⅡβ） in hippocampus CA1 area. METHODS： The rats were divided into 4 groups： sham group,VD group,VD ＋ Buyanghuanwu decoction group and VD ＋ nimodipine group. The VD rat model was prepared by Pulsinelli＇s four-vessel occlusion. At 7th day,14th day or 28th day after operation,the behaviors of the rats were tested by Morris water maze. The morphological changes of the neurons in hippocampus CA1 area were observed by HE staining 30 d after operation. Western blotting was used to observe the protein expression of ERK2 and CaMKⅡβ in the brain tissues of hippocampal CA1 area of the VD rats. RESULTS： Compared with sham group,the pathological changes such as irregular arrangement,coagulation necrosis and obvious deletion in the neurons of hippocampus CA1 area in VD group appeared significantly. The obstacle of learning and memory ability was observed and the protein expression of ERK2 and CaMKⅡβ in hippocampal CA1 area was significantly decreased （ P 0. 05） . Compared with VD group,the neurons in hippocampal CA1 area of VD ＋ Buyanghuanwu decoction group and VD ＋ nimodipine group were in eumorphism,lined up in order,and the structure was close to that in sham group. The ability of learning and memory also significantly improved （ P 0. 05） . The protein expression of ERK2 and CaMKⅡβ in hippocampal CA1 area significantly increased （ P 0. 05） . CONCLUSION： Buyanghuanwu decoction promotes the protein expression of ERK2 and CaMKⅡβ in hippocampus CA1 area to protect the neurons from injury,builds up the synapses and promotes the ability of learning and memory in VD rats.