化瘀祛痰方对血管性痴呆的保护作用机制探讨

闵冬雨; 张哲; 朱姝; 关乐; 鞠业涛; 王东妮; 曹媛; 杨关林

doi:10.13422/j.cnki.syfjx.20191539

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化瘀祛痰方对血管性痴呆的保护作用机制探讨

药理 | 更新时间：2021-02-09

- 化瘀祛痰方对血管性痴呆的保护作用机制探讨
- Study on Protective Effect of Huayu Qutan Decoction on Vascular Dementia
- 中国实验方剂学杂志 2019年25卷第16期页码：31-36
- 作者机构：
  
  1.辽宁中医药大学　附属医院，沈阳　 110032；
  2.中国医科大学　附属口腔医院，沈阳　 110031；
  3.辽宁中医药大学　中医脏象理论及应用教育部重点实验室，沈阳　 110847
- 作者简介：
  
  闵冬雨，博士，副主任药师，从事中西医结合心脑血管疾病防治研究，E-mail：mindongyu@163.com
  杨关林，主任医师，博士生导师，从事中西医结合临床研究，E-mail：guanli19621010@163.com
- 基金信息：
  
  国家重点基础研究发展计划（973计划）项目(2013CB531704);中国博士后科学基金项目(2014M551121);辽宁中医药大学中医脏象理论及应用国家教育部重点实验室项目(zyzx1705);辽宁省科技厅项目(20180551110)
- DOI：10.13422/j.cnki.syfjx.20191539
  中图分类号： R2-0; R285; R289; R74; R318.11
- 收稿日期：2018-11-06，
  
  网络出版日期：2019-04-19，
  
  纸质出版日期：2019-08-20
- 稿件说明：
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闵冬雨, 张哲, 朱姝, 等. 化瘀祛痰方对血管性痴呆的保护作用机制探讨[J]. 中国实验方剂学杂志, 2019,25(16):31-36.

Dong-yu MIN, Zhe ZHANG, Shu ZHU, et al. Study on Protective Effect of Huayu Qutan Decoction on Vascular Dementia[J]. Chinese journal of experimental traditional medical formulae, 2019, 25(16): 31-36.
闵冬雨, 张哲, 朱姝, 等. 化瘀祛痰方对血管性痴呆的保护作用机制探讨[J]. 中国实验方剂学杂志, 2019,25(16):31-36. DOI： 10.13422/j.cnki.syfjx.20191539.

Dong-yu MIN, Zhe ZHANG, Shu ZHU, et al. Study on Protective Effect of Huayu Qutan Decoction on Vascular Dementia[J]. Chinese journal of experimental traditional medical formulae, 2019, 25(16): 31-36. DOI： 10.13422/j.cnki.syfjx.20191539.

摘要

目的：

研究化瘀祛痰方对血管性痴呆(VD)沙鼠的保护作用，并初步探讨其作用机制是否与钙离子-钙调素依赖性蛋白激酶Ⅱ(CaMKⅡ)/环磷腺苷效应元件结合蛋白(CREB)/脑源性神经营养因子(BDNF)信号通路相关。

方法：

将健康沙鼠40只，随机分为假手术组，模型组，化瘀祛痰方低、中、高(5.35，10.7，21.4 g·kg

－1

)剂量组，每组8只，模型组及化瘀祛痰三组参考Levine法对全部沙鼠进行侧颈总动脉结扎再灌注法造VD模型；假手术组则不封闭颈部动脉，其他操作同手术组。术后沙鼠给予相应药物灌胃2次/日，21 d后进行水迷宫实验考察沙鼠的空间学习记忆能力。蛋白免疫印迹法(Western blot)及免疫组化分别测定沙鼠脑组织海马体的磷酸化(p)-CaMKⅡ/CaMKⅡ，p-CREB/CREB，BDNF蛋白的表达。

结果：

与假手术组比较，模型组沙鼠的上台潜伏期和平台穿梭次数明显降低，p-CaMKⅡ/CaMKⅡ，p-CREB/CREB，BDNF蛋白表达均明显降低(

0.01)；与模型组比较，化瘀祛痰方组沙鼠的上台潜伏期和平台穿梭次数明显升高，其中化瘀祛痰方中以高剂量组效果最为明显(

0.01)，化瘀祛痰方可以有效的保护CA1区锥体细胞，明显上调p-CaMKⅡ/CaMKⅡ，p-CREB/CREB，BDNF蛋白的表达(

0.01)。

结论：

化瘀祛痰方改善了血管性痴呆沙鼠的学习和记忆能力，作用机制可能与CaMKⅡ/CREB/BDNF信号通路的激活相关。

Abstract

Objective:

To study the protective effect of Huayu Qutan decoction on vascular dementia (VD) gerbils and to explore whether its mechanism is related to Calcium ion-calmodulin-dependent protein kinase Ⅱ (CaMKⅡ)/cyclic adenosine effect element binding protein (CREB)/brain-derived neurotrophic factor (BDNF) signaling pathway.

Method:

Forty healthy gerbils were randomly divided into sham operation group

model group

low

medium and high dose groups (5.35

10.7

21.4 g·kg

-1

) of removing blood stasis and expelling phlegm. Eight gerbils in each group were divided into model group and removing blood stasis and expelling phlegm group. Gerbils were given corresponding drugs twice a day after operation. Water maze experiment was conducted 21 days later to investigate the spatial learning and memory ability of gerbils. The expression of p-CaMKⅡ/CaMKⅡ

p-CREB/CREB and BDNF in the hippocampus of gerbils were detected by Western blot and immunohistochemistry.

Result:

Compared with sham operation group

the incubation period and the number of platform trips of gerbil in the model group were significantly reduced

p-CaMKⅡ/CaMKⅡ

p-CREB/CREB

and BDNF protein expression were significantly reduced (

0.01). Compared with model group

the incubation period and the number of platform shuttling of gerbil in Huayu Qutan decoction group were significantly increased

among which the high-dose phlegm dispelling prescription had the most significant effect (

0.01). The phlegm dispelling prescription could effectively protect pyramidal cells in CA1 region

significantly up-regulating the expression of p-CaMKⅡ/CaMKⅡ

p-CREB/CREB and BDNF protein (

0.01).

Conclusion:

Huayu Qutan decoction improves the learning and memory abilities of gerbils with vascular dementia

and its mechanism may be related to the activation of CaMKⅡ/CREB/BDNF signaling pathway.

关键词

Keywords

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