Effect of Modified Dihuang Yinzi on Learning and Memory Ability and Neuron Damage in Hippocampal CA1 Area in Rats with Vascular Dementia / 中国实验方剂学杂志

ABSTRACT

Objective:To observe the effect of modified Dihuang Yinzi on the learning and memory ability and on the neurons in CA1 area of hippocampus of rats suffering from vascular dementia. Method:The 84 male SD rats were randomly selected to form the sham operation group of 12 rats, and the other 72 rats were chosen for the vascular dementia model by means of Bivascular occlusion, and among which 60 were chosen randomly into 6 groups of 12 rats, namely, the model group, the nimodipine group (0.011 g·kg-1), and the high, medium and low dose modified Dihuang Yinzi (4.54, 2.27, 1.14 g·kg-1) respectively. After 30 days of continuous gavage, Morris water maze was used to detect the learning and memory ability of rats, hematoxylin eosin (HE) was used to observe the morphological changes of hippocampal CA1 neurons, transmission electron microscopy was used to observe the ultrastructural changes of hippocampal CA1 neurons, TUNEL was used to detect the apoptosis level of hippocampal CA1 neurons, immunohistochemical(IHC) was used to detect the expression level of phosphatidylinositol-3(PI3K), protein kinase B (Akt), Caspase-3 in hippocampal CA1 tissues. Result:Compared with sham operation group, the escape latency of the model group was significantly prolonged, the number of times of crossing the original platform was significantly reduced (P<0.01), the neuronal morphology of hippocampal CA1 area was damaged to varying degrees, the apoptosis rate was significantly increased (P<0.01), the integral optical density and average optical density of PI3K, Akt were significantly reduced (P<0.01), and the integral optical density and average optical density of Caspase-3 were significantly reduced (P<0.01). Compared with model group, the escape latency was shortened (P<0.05, P<0.01), the number of crossing the original platform was increased (P<0.05, P<0.01), the integrated optical density and average optical density of PI3K and Akt were significantly increased (P<0.01), and the integrated optical density and average optical density of Caspase-3 were decreased in different degrees (P<0.05, P<0.01). Conclusion:Modified Dihuang Yinzi can improve the learning and memory ability of vascular dementia model rats and the damaged neurons in the hippocampal CA1 area. The potential mechanism may be related to the activation of PI3K/Akt signal transduction pathway and the inhibition of apoptosis of neurons in hippocampal CA1 area of rats.