养心生脉颗粒对冠心病伴焦虑抑郁大鼠的干预作用及机制研究

张明倩; 崔爽; 梁五林; 张天睿; 郭凡帆; 欧文静; 伍永鸿; 黄喜燕; 贾占红; 张仲毅; 卢凤华; 张硕峰

doi:10.3969/j.issn.1006-2157.2022.02.008

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养心生脉颗粒对冠心病伴焦虑抑郁大鼠的干预作用及机制研究

中药药理 | 更新时间：2022-08-25

- 养心生脉颗粒对冠心病伴焦虑抑郁大鼠的干预作用及机制研究
- Intervention effect and mechanism of Yangxin Shengmai Granule on rats with coronary heart disease with anxiety and depression
- 北京中医药大学学报 2022年45卷第8期页码：806-814
- 作者机构：
  
  1.北京中医药大学中药学院　北京　102488
  2.秦皇岛市山海关药业有限责任公司
- 作者简介：
  
  张明倩，女，在读硕士生
  #张硕峰，男，博士，教授，博士生导师，主要研究方向：中医药防治心脑血管疾病的研究，E-mail：shuofengzhang@sina.com
- 基金信息：
  
  国家科技重大专项项目(2014ZX09304306);北京市自然科学基金项目(7144222)
- DOI：10.3969/j.issn.1006-2157.2022.02.008
  中图分类号： R285.5
- 收稿：2022-01-05，
  
  网络首发：2022-06-24，
  
  纸质出版：2022-08-30
- 稿件说明：
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张明倩, 崔爽, 梁五林, 等. 养心生脉颗粒对冠心病伴焦虑抑郁大鼠的干预作用及机制研究[J]. 北京中医药大学学报, 2022,45(8):806-814.

Mingqian ZHANG, Shuang CUI, Wulin LIANG, et al. Intervention effect and mechanism of Yangxin Shengmai Granule on rats with coronary heart disease with anxiety and depression[J]. Journal of Beijing University of Traditional Chinese Medicine, 2022, 45(8): 806-814. DOI: 10.3969/j.issn.1006-2157.2022.02.008.
张明倩, 崔爽, 梁五林, 等. 养心生脉颗粒对冠心病伴焦虑抑郁大鼠的干预作用及机制研究[J]. 北京中医药大学学报, 2022,45(8):806-814. DOI： 10.3969/j.issn.1006-2157.2022.02.008.

Mingqian ZHANG, Shuang CUI, Wulin LIANG, et al. Intervention effect and mechanism of Yangxin Shengmai Granule on rats with coronary heart disease with anxiety and depression[J]. Journal of Beijing University of Traditional Chinese Medicine, 2022, 45(8): 806-814. DOI: 10.3969/j.issn.1006-2157.2022.02.008. DOI：

摘要

目的

探讨养心生脉颗粒通过脑源性神经营养因子(BDNF)/TrκB通路对冠心病伴焦虑抑郁大鼠的影响。

方法

SD大鼠124只任意分为空白组14只和造模组110只，除空白组外，其余各组采用孤养加慢性不可预见性温和应激(CUMS)建立大鼠抑郁模型，持续28 d，于第15天结扎冠状动脉左前降支建立心肌缺血再灌注模型。其中14只大鼠手术但不结扎为假手术组；造模成功大鼠随机分为模型组，养心生脉颗粒低、中、高剂量(2.1、4.2、8.4 g/kg)组及复方丹参片(0.29 g/kg)联合氟西汀(0.01 g/kg)组，结扎术后第2天开始各组灌胃蒸馏水或相应药液。灌胃给药2周后对各组大鼠进行行为学检测，HE染色观察心肌组织损伤情况及左室内径和左室壁厚度，免疫组化法检测心肌组织BDNF、TrκB、CD34蛋白表达，Western blotting检测大鼠海马组织BDNF、TrκB、p-TrκB蛋白表达水平。

结果

与假手术组相比，模型组大鼠进入旷场中心区域的次数、时间以及运动轨迹总路程降低，差异有统计学意义(

0.01)，在高架十字迷宫开放臂滞留次数和时间比例减少，差异有统计学意义(

0.01)；与模型组相比，各给药组大鼠进入旷场中心区域的次数、时间以及运动轨迹总路程升高，差异有统计学意义(

0.01)，高架十字迷宫开放臂滞留次数和时间比例增加，但差异无统计学意义。与假手术组相比，模型组大鼠心肌组织损伤程度加重、左室内径增加(

0.01)，左室壁厚度和心肌组织BDNF、TrκB、CD34蛋白水平以及海马组织BDNF、p-TrκB/TrκB蛋白水平降低，差异有统计学意义(

0.05，

0.01)；与模型组比较，各给药组大鼠心肌损伤程度改善，左室内径减小(

0.01)，左室壁厚度和心肌组织BDNF、TrκB、CD34蛋白水平以及海马组织BDNF、p-TrκB/TrκB蛋白水平升高，差异有统计学意义(

0.05，

0.01)。

结论

养心生脉颗粒能够改善冠心病伴焦虑抑郁大鼠的心脏功能和抑郁症状，可能通过激活BDNF/TrκB信号通路发挥心脏保护作用和抗抑郁作用。

Abstract

Objective

To investigate the effect of

Yangxin Shengmai

(Heart-nourishing Pulse-engendering) Granule (YXSM Granule) on rats with coronary heart disease complicated with anxiety and depression through BDNF/TrκB pathway.

Methods

124 SD rats were randomly divided into the blank group (

=14) and the model group (

=110). Except for the blank group

the depression model was established with Chronic Unpredictable Mild Stress (CUMS) for 28 days. On the 15th day

the myocardial infarction reperfusion model was established by ligating the left anterior descending coronary artery. Among the rat models

14 rats were operated but not ligated

and they were set as the sham operation group; the others were randomly divided into model group and low-

medium- and high-dose (2.1

4.2

8.4 g/kg) YXSM Granule groups and 0.29 g/kg Compound Danshen tablet + Fluoxetine (CDST+ Flu) group. After intragastric administration for 2 weeks

the rats in each group undergone behavioral tests. The myocardial injury

left ventricle diameter (LVD) and left ventricular wall thickness (LVWT) were observed by HE staining

the protein expression levels of BDNF

TrκB and CD34 in myocardial tissue were detected by immunohistochemistry

and the protein expression levels of BDNF

TrκB and p-TrκB in hippocampus were detected by Western blotting.

Results

Compared with the sham group

the frequency of entering the central area of the open field and the total time spent and total distance travelled in the movement track in the model group were significantly reduced (

0.01)

and the frequency and proportion of time spent in the open arm of the elevated cross maze were significantly reduced. Compared with the model group

the frequency of entering the central area of the open field and the total time spent and distance travelled in the movement track in all YXSM Granule groups and CDST+ Flu group were significantly increased (

0.01)

and the frequency and proportion of time spent in the open arm of the elevated cross maze were significantly increased

but with no significant difference. Compared with the sham operation group

in the model group

the degree of myocardial injury and LVD were significantly increased (

0.01)

the LVWT and the protein expression levels of BDNF

TrκB and CD34 in myocardial tissue and BDNF and p-trkb/TrκB in hippocampus decreased significantly (

0.05

0.01). Compared with the model group

the degree of myocardial injury was significantly improved

the LVD was significantly reduced (

0.01)

the LVWT and the protein expression levels of BDNF

TrκB and CD34 in myocardial tissue and BDNF and p-TrκB/TrκB in hippocampus were significantly increased (

0.05

0.01) in all the other groups.

Conclusion

YXSM Granule seems to improve the cardiac function and alleviate depressive symptoms in rats with coronary heart disease with anxiety and depression

which may play a cardioprotective and antidepressant role by activating BDNF/TrκB signal pathway.

关键词

Keywords

references

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