Effects of <italic style="font-style: italic">Naoluoxintong</italic> and its Disassembled Prescriptions on Learning and Memory Ability and Synaptic Plasticity in Right Middle Cerebral Artery Occlusion-reperfusion Rats

Xuemei QIN; Peipei LI; Xiao SHI; Lina WANG; Gen JIA; Jianpeng HU

doi:10.13288/j.11-2166/r.2022.12.012

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Effects of Naoluoxintong and its Disassembled Prescriptions on Learning and Memory Ability and Synaptic Plasticity in Right Middle Cerebral Artery Occlusion-reperfusion Rats

更新时间：2022-06-10

- Effects of Naoluoxintong and its Disassembled Prescriptions on Learning and Memory Ability and Synaptic Plasticity in Right Middle Cerebral Artery Occlusion-reperfusion Rats
- Journal of Traditional Chinese Medicine Vol. 63, Issue 12, Pages: 1163-1169(2022)
- 作者机构：
  
  1.安徽中医药大学中医学院，安徽省合肥市蜀山区梅山路103号，230038
  2.徐州医科大学附属邳州医院
- 作者简介：
- 基金信息：
- DOI：10.13288/j.11-2166/r.2022.12.012
  CLC：
- Received：25 September 2021，
  
  Revised：2022-01-21，
  
  Published：17 June 2022
- 稿件说明：
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秦雪梅,李佩佩,时潇等.脑络欣通及其拆方对右侧大脑中动脉闭塞再灌注大鼠学习记忆能力及突触可塑性的影响[J].中医杂志,2022,63(12):1163-1169.

QIN Xuemei,LI Peipei,SHI Xiao,et al.Effects of Naoluoxintong and its Disassembled Prescriptions on Learning and Memory Ability and Synaptic Plasticity in Right Middle Cerebral Artery Occlusion-reperfusion Rats[J].Journal of Traditional Chinese Medicine,2022,63(12):1163-1169.
秦雪梅,李佩佩,时潇等.脑络欣通及其拆方对右侧大脑中动脉闭塞再灌注大鼠学习记忆能力及突触可塑性的影响[J].中医杂志,2022,63(12):1163-1169. DOI： 10.13288/j.11-2166/r.2022.12.012.

QIN Xuemei,LI Peipei,SHI Xiao,et al.Effects of Naoluoxintong and its Disassembled Prescriptions on Learning and Memory Ability and Synaptic Plasticity in Right Middle Cerebral Artery Occlusion-reperfusion Rats[J].Journal of Traditional Chinese Medicine,2022,63(12):1163-1169. DOI： 10.13288/j.11-2166/r.2022.12.012.

摘要

目的

探讨脑络欣通防治缺血性脑卒中的可能作用机制。

方法

50只SD大鼠随机分为假手术组、模型组、脑络欣通组、益气组、活血通络组各10只。除假手术组外，其余各组大鼠采用改良线栓法制造大鼠右侧大脑中动脉缺血再灌注模型。造模成功后，脑络欣通组、益气组、活血通络组大鼠分别给予脑络欣通8.54 g/（kg·d）、益气方3.5 g/（kg·d）、活血通络方5.04 g/（kg·d）灌胃，假手术组和模型组大鼠均给予10 ml/（kg·d）的生理盐水灌胃，每日2次，共灌胃14天。采用Morris水迷宫（定位航行实验、空间探索实验）观察大鼠学习记忆能力，HE染色观察右侧额顶叶皮质及海马区病理学变化，免疫组化观察右侧额顶叶皮质和海马区谷氨酸受体1（GluR1）、钙/钙调素依赖性蛋白激酶Ⅱ（CaMKⅡ）表达变化。

结果

与假手术组比较，模型组大鼠各时间点逃避潜伏期均显著延长，在目标象限停留的时间及穿越平台的次数均减少，右侧额顶叶皮质及海马区GluR1、CaMKⅡ表达降低（

＜0.01）；与模型组比较，脑络欣通组、益气组、活血通络组大鼠各时间点逃避潜伏期均显著缩短（

＜0.05），在目标象限停留的时间及穿越平台的次数明显增多（

＜0.05），右侧额顶叶皮质及海马区GluR1、CaMKⅡ表达升高（

＜0.01）；与脑络欣通组比较，益气组、活血通络组大鼠各时间点逃避潜伏期延长，在目标象限停留的时间及穿越平台的次数减少，右侧额顶叶皮质及海马区GluR1、CaMKⅡ表达降低（

＜0.05）。益气组和活血通络组各指标表达差异均无统计学意义（

＞0.05）。组织病理学结果显示，与模型组相比，脑络欣通组、益气组、活血通络组神经细胞排列、形态大小均有所恢复，细胞水肿、坏死等现象改善。脑络欣通组比益气组、活血通络组改善病理损伤现象更明显。

结论

脑络欣通可改善右侧大脑中动脉闭塞再灌注大鼠学习记忆能力，全方效果优于各拆方，其作用机制可能与促进额顶叶皮质及海马区GluR1、CaMKⅡ蛋白表达，从而提高突触可塑性有关。

Abstract

Objective

To explore the possible mechanism of Naoluoxintong （脑络欣通） for prevention and treatment of ischemic stroke.

Methods

Fifty SD rats were randomly divided into sham operation group， model group，

Naoluoxintong

group，

Yiqi

（益气） group and

Huoxue Tongluo

（活血通络） group， with 10 rats in each group. Except for the sham operation group， the modified suture method was used in the other groups to establish the right middle cerebral ischemia-reperfusion model. After successful modeling， rats in the

Naoluoxintong

group，

Yiqi

group and

Huoxue Tongluo

group were given

Naoluoxintong

8.54 g/（kg·d），

Yiqi

Formula

3.5 g（kg·d） and

Huoxue Tongluo Formula

5.04 g/（kg·d） by gavage respectively， while the sham operation group and the model group were given the 10 ml/（kg·d） of normal saline by gavage， twice a day， for a total of 14 days. Morris water maze （positioning navigation test， spatial navigation test） was used to observe the learning and memory ability of rats， while HE staining was used to observe the pathological changes in the right frontoparietal cortex and hippocampus， and immunohistochemistry was used to detect changes in the expression of glutamate receptor 1 （GluR1） and calcium/calmodulin-dependent protein kinase Ⅱ （CaMKⅡ） in the right frontoparietal cortex and hippocampus.

Results

Compared with those in the sham operation group， the escape latency of rats in the model group was significantly prolonged at each time point， while the time spent in the target quadrant and the times of crossing the platform decreased， and the expressions of GluR1 and CaMKⅡ were reduced （

＜0.01）. Compared with those in the model group， the escape latency of the rats in the

Naoluoxintong

group， the

Yiqi

group and the

Huoxue Tongluo

group at each time point was significantly shortened （

＜0.05）， while the time spent in the target quadrant and the times of crossing the platform increased significantly （

＜0.05）， and the expressions of GluR1 and CaMKII increased as well （

＜0.01）. Compared with those in the

Naoluoxintong

group， the escape latency in the

Yiqi

group and the

Huoxue Tongluo

group was prolonged at each time point， while the time spent in the target quadrant and the times of crossing the platform decreased， and the expression of GluR1 and CaMKⅡ were reduced （

＜0.05）. There were no significant differences in the expression of all indicators between the

Yiq

i group and the

Huoxue Tongluo

group （

＞0.05）. The histopathological results showed that compared with those in the model group， the arrangement， shape and size of nerve cells in the

Naoluoxintong

group， the

Yiqi

group and the

Huoxue Tongluo

group were restored， and the cell edema and necrosis were improved， with more significant improvement in the

Naoluoxintong

group.

Conclusion

Naoluoxintong

can improve the ability of learning and memory in right middle cerebral artery occlusion-reperfusion rats， and the overall effect is better than its disassembled prescriptions. The mechanism may be related to the promotion of the expression of GluR1 and CaMKⅡ proteins in the fronto-parietal cortex and hippocampus， thereby enhancing synaptic plasticity.

关键词

Keywords

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Effects of Naoluoxintong and its Disassembled Prescriptions on Learning and Memory Ability and Synaptic Plasticity in Right Middle Cerebral Artery Occlusion-reperfusion Rats

DOI：10.13288/j.11-2166/r.2022.12.012

摘要

Abstract

关键词

Keywords

references