Effect of Modified Dihuang Yinzi on Learning and Memory Ability and Neuron Damage in Hippocampal CA1 Area in Rats with Vascular Dementia

Yu-hui ZHOU; Ming-san MIAO; Meng LU; Jin-dong GUO; Bo-wen WU; Xiao-ning LI; Wei-juan GAO; Mi-shan WU

doi:10.13422/j.cnki.syfjx.20200836

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Effect of Modified Dihuang Yinzi on Learning and Memory Ability and Neuron Damage in Hippocampal CA1 Area in Rats with Vascular Dementia

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- Effect of Modified Dihuang Yinzi on Learning and Memory Ability and Neuron Damage in Hippocampal CA1 Area in Rats with Vascular Dementia
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 26, Issue 8, Pages: 53-61(2020)
- 作者机构：
  
  1.河北中医学院　基础医学院　方剂学教研室，石家庄　 050200
  2.河南中医药大学，郑州　 450046
  3.河北省心脑血管病中医药防治研究重点实验室，石家庄　 050091
- 作者简介：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.20200836
  CLC： R2-0; R289; R285.5
- Received：17 October 2019，
  
  Published Online：04 January 2020，
  
  Published：20 April 2020
- 稿件说明：
移动端阅览
Yu-hui ZHOU, Ming-san MIAO, Meng LU, et al. Effect of Modified Dihuang Yinzi on Learning and Memory Ability and Neuron Damage in Hippocampal CA1 Area in Rats with Vascular Dementia[J]. Chinese journal of experimental traditional medical formulae, 2020, 26(8): 53-61.
DOI：

Yu-hui ZHOU, Ming-san MIAO, Meng LU, et al. Effect of Modified Dihuang Yinzi on Learning and Memory Ability and Neuron Damage in Hippocampal CA1 Area in Rats with Vascular Dementia[J]. Chinese journal of experimental traditional medical formulae, 2020, 26(8): 53-61. DOI： 10.13422/j.cnki.syfjx.20200836.

摘要

目的：

观察地黄饮子加减方对血管性痴呆模型大鼠学习记忆能力及海马CA1区神经元的影响。

方法：

将84只SD雄性大鼠，按随机原则选出12只大鼠作为假手术组，其余72只大鼠采用两血管阻断法制备血管性痴呆模型，筛选60只模型大鼠，每组12只，随机分为模型组，尼莫地平组(0.011 g·kg

-1

)，地黄饮子加减方高、中、低(4.54，2.27，1.14 g·kg

-1

)剂量组。连续灌胃30 d后，Morris水迷宫检测大鼠学习记忆能力，苏木素-伊红(HE)观察海马CA1区神经元形态结构改变，透射电镜观察海马CA1区神经元超微结构变化，原位细胞凋亡检测法(TUNEL)检测海马CA1区细胞凋亡水平，免疫组化(IHC)检测海马CA1区组织磷脂酰肌醇3-激酶(PI3K)，蛋白激酶B(Akt)，半胱氨酸蛋白酶-3(Caspase-3)表达水平。

结果：

与假手术组比较，模型组大鼠逃避潜伏期显著延长，穿越原平台次数显著减少(

0.01)，海马CA1区神经元形态均有不同程度地损伤，凋亡率显著增加(

0.01)，PI3K，Akt的积分吸光度和平均积分吸光度明显降低(

0.01)，Caspase-3的积分吸光度和平均积分吸光度显著增高(

0.01)；与模型组比较，各给药组大鼠逃避潜伏期缩短(

0.05，

0.01)，穿越原平台次数增加(

0.05，

0.01)，PI3K，Akt的积分吸光度和平均积分吸光度值显著增高(

0.01)，Caspase-3的积分光密度和平均积分吸光度不同程度降低(

0.05，

0.01)。

结论：

地黄饮子加减方可改善血管性痴呆模型大鼠学习记忆能力和海马CA1区神经元损伤，潜在机制可能与PI3K/Akt信号转导途径的激活，抑制大鼠海马CA1区神经细胞的凋亡有关。

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 (

0.01)

the neuronal morphology of hippocampal CA1 area was damaged to varying degrees

the apoptosis rate was significantly increased (

0.01)

the integral optical density and average optical density of PI3K

Akt were significantly reduced (

0.01)

and the integral optical density and average optical density of Caspase-3 were significantly reduced (

0.01). Compared with model group

the escape latency was shortened (

0.05

0.01)

the number of crossing the original platform was increased (

0.05

0.01)

the integrated optical density and average optical density of PI3K and Akt were significantly increased (

0.01)

and the integrated optical density and average optical density of Caspase-3 were decreased in different degrees (

0.05

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.

关键词

Keywords

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