Effect of Wuzang Wenyang Huayu Decoction on Neurofibrillary Tangles by Inhibiting Cyclin-dependent Kinase-5 Over-expression in SAMP8 Mice

Wei NONG; Zhi-quan WEI; Xue-ni MO; Lin WU; Nong TANG

doi:10.13422/j.cnki.syfjx.20190839

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Effect of Wuzang Wenyang Huayu Decoction on Neurofibrillary Tangles by Inhibiting Cyclin-dependent Kinase-5 Over-expression in SAMP8 Mice

Pharmacology | 更新时间：2021-02-09

- Effect of Wuzang Wenyang Huayu Decoction on Neurofibrillary Tangles by Inhibiting Cyclin-dependent Kinase-5 Over-expression in SAMP8 Mice
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 25, Issue 9, Pages: 61-66(2019)
- 作者机构：
  
  广西中医药大学　广西中医基础研究重点实验室，南宁　 530001
- 作者简介：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.20190839
  CLC： R289; R745.1; R944.6+ 1; R285.5
- Received：01 November 2018，
  
  Published Online：04 January 2019，
  
  Published：05 May 2019
- 稿件说明：
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Wei NONG, Zhi-quan WEI, Xue-ni MO, et al. Effect of Wuzang Wenyang Huayu Decoction on Neurofibrillary Tangles by Inhibiting Cyclin-dependent Kinase-5 Over-expression in SAMP8 Mice[J]. Chinese journal of experimental traditional medical formulae, 2019, 25(9): 61-66.
DOI：

Wei NONG, Zhi-quan WEI, Xue-ni MO, et al. Effect of Wuzang Wenyang Huayu Decoction on Neurofibrillary Tangles by Inhibiting Cyclin-dependent Kinase-5 Over-expression in SAMP8 Mice[J]. Chinese journal of experimental traditional medical formulae, 2019, 25(9): 61-66. DOI： 10.13422/j.cnki.syfjx.20190839.

摘要

目的：

探讨五脏温阳化瘀汤改善SAMP8小鼠认知能力的周期蛋白依赖性激酶-5(CDK-5)相关脑神经纤维缠结机制。

方法：

10只SAMR1小鼠为正常组，40只SAMP8小鼠随机分为模型组，多奈哌齐组(0.4 mg·kg

－1

·d

－1

)，五脏温阳化瘀汤高、低剂量组(5，1.25 g·kg

－1

·d

－1

)，连续灌胃给药4周。Morris水迷宫测试定位航行与空间探索能力；实时荧光定量聚合酶链式反应(Real-time PCR)检测脑神经组织CDK-5 mRNA表达水平；蛋白免疫印迹法(Western blot)检测脑神经组织CDK-5蛋白表达与Tau蛋白磷酸化水平；银染法检测脑神经纤维缠结。

结果：

与正常组比较，模型组脑神经组织CDK-5与Tau蛋白磷酸化表达水平均显著升高(

0.01)，脑神经纤维缠结明显增多，定位航行与空间探索能力显著减弱(

0.01)；与模型组比较，五脏温阳化瘀汤高、低剂量组脑神经组织CDK-5与Tau蛋白磷酸化表达水平均明显降低(

0.05，

0.01)，脑神经纤维缠结减少，小鼠定位航行并空间探索能力明显改善(

0.05，

0.01)。

结论：

五脏温阳化瘀汤可显著改善SAMP8小鼠认知能力，可能与其抑制CDK-5过表达进而抑制Tau蛋白过磷酸化导致脑神经纤维缠结减少有关。

Abstract

Objective:

To explore the mechanism of Wuzang Wenyang Huayu decoction in improving the cognitive competence and the pharmacological mechanism for neurofibrillary tangles related to cyclin-dependent kinase-5 (CDK-5).

Method:

The 10 SAMR1 mice were used as normal group

40 SAMP8 mice were randomly divided into model group

donepezil group (0.4 mg·kg

-1

·d

-1

)

high and low dose Wuzang Wenyang Huayu decoction groups (5

1.25 g·kg

-1

·d

-1

). Drugs were administered by gastric lavage for 4 continuous weeks. Directional navigation and space exploration ability were evaluated with Morris amaze. Real-time PCR was used to measure the mRNA expression of CDK-5 in brain nerve tissues.Western blot was used to detect the protein expression of CDK-5 and phosphorylation of Tau protein. Meanwhile

neurofibrillary tangles in brain tissue were detected with silver staining method.

Result:

As compared with normal group

both CDK-5 expression and Tau protein phosphorylation in brain nerve tissues were remarkably increased in model group (

0.01)

with significantly increased neurofibrillary tangles and significantly decreased directional navigation ability and space exploration ability (

0.01). As compared with model group

CDK-5 expression and Tau protein phosphorylation were lower in Wuzang Wenyang Huayu decoction treated groups(

0.05

0.01)

accompanied by decreased number of neurofibrillary tangles as well as improved directional navigation and space exploration ability(

0.05

0.01).

Conclusion:

Wuzang Wenyang Huayu decoction can markedly improve the cognitive competence of SAMP8 mice

and the mechanism may be related to its inhibition on CDK-5 over-expression

and down-regulation of Tau protein phosphorylation and neurofibrillary tangles in brain tissue.

关键词

Keywords

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