Yixin Ningshen Tablet Alleviates Comorbidity of Myocardial Infarction and Depression by Enhancing Myocardial Energy Metabolism and Increasing Availability of Monoamine Neurotransmitter

Bing JIANG; Ruo-ming WU; Hai-dong LI; Kun LI; Hui LI; Wen-zhen DANG; Gui-ze FENG; Wei-lian BAO; Guan YE; Xiao-yan SHEN

doi:10.1007/s11655-022-3570-3

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Yixin Ningshen Tablet Alleviates Comorbidity of Myocardial Infarction and Depression by Enhancing Myocardial Energy Metabolism and Increasing Availability of Monoamine Neurotransmitter

Original Article | Updated：2022-06-27

- Yixin Ningshen Tablet Alleviates Comorbidity of Myocardial Infarction and Depression by Enhancing Myocardial Energy Metabolism and Increasing Availability of Monoamine Neurotransmitter
- Chinese Journal of Integrative Medicine Vol. 28, Issue 7, Pages: 586-593(2022)
- Affiliations：
  
  1.Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai (200120), China
  2.Department of Pharmacology of Chinese Materia Medica, School of Traditional Chinese Medicine, Guangdong Pharmaceutical University,Guangzhou (510006), China
  3.Central Research Institute,Shanghai Pharmaceuticals Holding Co., Ltd., Shanghai(200120), China
- Author bio：
  
  Dr. SHEN Xiao-yan, E-mail: shxiaoy@fudan.edu.cn
- Funds：
- DOI：10.1007/s11655-022-3570-3
  CLC：
- Published：01 July 2022，
  
  Published Online：23 March 2022，
  
  Accepted：11 November 2021
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Bing JIANG, Ruo-ming WU, Hai-dong LI, et al. Yixin Ningshen Tablet Alleviates Comorbidity of Myocardial Infarction and Depression by Enhancing Myocardial Energy Metabolism and Increasing Availability of Monoamine Neurotransmitter. [J]. Chinese Journal of Integrative Medicine 28(7):586-593(2022)
DOI：

Bing JIANG, Ruo-ming WU, Hai-dong LI, et al. Yixin Ningshen Tablet Alleviates Comorbidity of Myocardial Infarction and Depression by Enhancing Myocardial Energy Metabolism and Increasing Availability of Monoamine Neurotransmitter. [J]. Chinese Journal of Integrative Medicine 28(7):586-593(2022) DOI： 10.1007/s11655-022-3570-3.

摘要

目的:

研究益心宁神片 (YXNS) 对大鼠心肌梗死 (MI) 合并抑郁的治疗作用及机制.

方法:

SD大鼠按体重随机分为5组

分别为对照组、模型组、氟西汀 (FLXT

10 mg/kg) 、低剂量YXNS (LYXNS

100 mg/kg) 和高剂量YXNS (HYXNS

300 mg/kg) 组

每组8只. 通过结扎左冠状动脉前降支

慢性轻度应激

建立大鼠心肌梗死抑郁共病模型. 所有大鼠用相应药物预处理12周后

进行超声心动图、蔗糖偏好试验、旷场试验和强迫游泳试验. 同时检测心肌梗死面积和心肌细胞凋亡. 采用酶联免疫吸附法测定血清白细胞介素 (IL) -6、IL-1β、肿瘤坏死因子-α (TNF-α) 、5-羟色胺 (5-HT) 、促肾上腺皮质激素 (ACTH) 、皮质酮 (CORT) 和去甲肾上腺素 (NE) 水平. Western blot分析检测心脏中5’-单磷酸腺苷激活蛋白激酶 (AMPK) 、p-AMPK、过氧化物酶体增殖物激活受体γ-辅激活因子-1α (PGC-1α) 和核呼吸因子1 (NRF1) 的蛋白. 实时定量聚合酶链反应检测肿瘤坏死因子-α、白介素-6、吲哚胺2

3-双加氧酶 (IDO1) 、犬尿氨酸3-单加氧酶 (KMO) 和犬尿氨酸酶 (KYNU) 的表达水平.

结果:

与模型组相比

YXNS组大鼠心功能明显改善 (

0.01) . 同时

YXNS能有效减少心肌梗死面积和心肌细胞凋亡 (

0.01或

0.05)

促进AMPK磷酸化

增加PGC-1α (

0.01) . YXNS显著提高大鼠的运动活性

降低TNF-α、IL-6和IL-1β的水平

并提高血清5-HT、NE、ACTH和CORT的水平 (均

0.05) . 此外

HYXNS降低IDO1、KMO和KYNU的mRNA表达 (

0.05) .

结论:

YXNS能通过增强心肌能量代谢来缓解心肌梗死. 同时

YXNS可以通过抗炎和增加单胺类神经递质的可用性来缓解抑郁. 它可能被用作治疗MI和抑郁症共病的潜在药物.

Abstract

Objective:

To investigate the therapeutic effect of Yixin Ningshen Tablet (YXNS) on comorbidity of myocardial infarction (MI) and depression in rats and explore the underlying mechanism.

Methods:

The Sprague-Dawley rats were randomly divided into 5 groups with 7 rats in each group according to their weights

including control

model

fluoxetine (FLXT

10 mg/kg)

low-dose YXNS (LYXNS

100 mg/kg)

and high-dose YXNS (HYXNS

300 mg/kg) groups. All rats were pretreated with corresponding drugs for 12 weeks. The rat model of MI and depression was constructed by ligation of left anterior descending coronary artery and chronic mild stress stimulation. The echocardiography

sucrose preference test

open field test

and forced swim test were performed. Myocardial infarction (MI) area and myocardial apoptosis was also detected. Serum levels of interleukin (IL)-6

IL-1β

tumor necrosis factor-α (TNF-α)

5-hydroxytryptamine (5-HT)

adrenocorticotrophic hormone (ACTH)

corticosterone (CORT)

and norepinephrine (NE) were determined by enzyme linked immunosorbent assay. The proteins of adenosine 5'-monophosphate -activated protein kinase (AMPK)

p-AMPK

peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α)

and nuclear respiratory factor 1 (NRF1) in heart were detected by Western blot analysis. The expression levels of TNF-α

IL-6

indoleamine 2

3-dioxygenase (IDO1)

kynurenine 3-monooxygenase (KMO)

and kynureninase (KYNU) in hippocampus were detected by real-time quantitative polymerase chain reaction.

Results:

Compared with the model group

the cardiac function of rats treated with YXNS significantly improved (

0.01). Meanwhile

YXNS effectively reduced MI size and cardiomyocytes apoptosis of rats (

0.01 or

0.05)

promoted AMPK phosphorylation

and increased PGC-1α protein expression (

0.01 or

0.05). HYXNS significantly increased locomotor activity of rats

decreased the levels of TNF-α

IL-6 and IL-1β

and increased the serum levels of 5-HT

ACTH

and CORT (all

0.05). Moreover

HYXNS decreased the mRNA expressions of IDO1

KMO and KYNU (

0.05).

Conclusions:

YXNS can relieve MI by enhancing myocardial energy metabolism. Meanwhile

YXNS can alleviate depression by resisting inflammation and increasing availability of monoamine neurotransmitters. It may be used as a potential drug to treat comorbidity of MI and depression.

关键词

Keywords

Yixin Ningshen Tabletdepressioncardiovascular disordersinflammatory factormonoamine neurotransmitterkynurenine pathwayChinese medicine

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