益心宁神片通过提高心肌能量代谢和单胺类神经递质的利用率缓解心肌梗死和抑郁的共病

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

Your Location：

Home >

Browse articles >

益心宁神片通过提高心肌能量代谢和单胺类神经递质的利用率缓解心肌梗死和抑郁的共病

Original Article | Updated：2022-06-27

- 益心宁神片通过提高心肌能量代谢和单胺类神经递质的利用率缓解心肌梗死和抑郁的共病
- 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 2022年28卷第7期页码：586-593
- 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：
  
  the Science and Technology Commission of Shanghai Municipality(15DZ1900103;15DZ1900100)
- DOI：10.1007/s11655-022-3570-3
  中图分类号：
- 纸质出版日期：2022-07-01，
  
  网络出版日期：2022-03-23，
  
  录用日期：2021-11-11
Scan for full text
Bing JIANG, Ruo-ming WU, Hai-dong LI, 等. 益心宁神片通过提高心肌能量代谢和单胺类神经递质的利用率缓解心肌梗死和抑郁的共病[J]. Chinese Journal of Integrative Medicine, 2022,28(7):586-593.

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, 2022,28(7):586-593.
Bing JIANG, Ruo-ming WU, Hai-dong LI, 等. 益心宁神片通过提高心肌能量代谢和单胺类神经递质的利用率缓解心肌梗死和抑郁的共病[J]. Chinese Journal of Integrative Medicine, 2022,28(7):586-593. DOI： 10.1007/s11655-022-3570-3.

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, 2022,28(7):586-593. 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

references

Liu MY, Ren YP, Zhang LJ, Ding JY. Pretreatment with ginseng fruit saponins affects serotonin expression in an experimental comorbidity model of myocardial infarction and depression. Aging Dis 2016;7:680-686.

Carney RM, Freedland KE. Depression, mortality, and medical morbidity in patients with coronary heart disease.Biol Psychiatry 2003;54:241-247.

Cooney MT, Kotseva K, Dudina A, De Backer G,Wood D, Graham I. Determinants of risk factor control in subjects with coronary heart disease: a report from the EUROASPIRE Ⅲ investigators. Eur J Prev Cardiol 2013;20:686-691.

Thombs BD, Bass EB, Ford DE, Stewart KJ, Tsilidis KK,Patel U, et al. Prevalence of depression in survivors of acute myocardial infarction. J Gen Intern Med 2006;21:30-38.

Williams MS. Platelets and depression in cardiovascular disease: a brief review of the current literature. World J Psychiatry 2012;2:114-123.

Glassman A. Depression and cardiovascular disease.Pharmacopsychiatry 2008;41:221-225.

Glassman AH, Bigger Jr JT, Gaffney M. Psychiatric characteristics associated with long-term mortality among 361 patients having an acute coronary syndrome and major depression: seven-year follow-up of SADHART participants.Arch Gen Psychiatry 2009;66:1022-1029.

Whooley MA, Wong JM. Depression and cardiovascular disorders. Annu Rev Clin Psychol 2013;9:327-354.

Seligman F, Nemeroff CB. The interface of depression and cardiovascular disease: therapeutic implications. Ann N Y Acad Sci 2015;1345:25-35.

Kim HJ, Kim P, Shin CY. A comprehensive review of the therapeutic and pharmacological effects of ginseng and ginsenosides in central nervous system. J Ginseng Res 2013;37:8-29.

Lee CH, Kim JH. A review on the medicinal potentials of ginseng and ginsenosides on cardiovascular diseases. J Ginseng Res 2014;38:161-166.

Shi SB, Liang JJ, Liu T, Yuan XR, Ruan Bi, Sun LF, et al.Depression increases sympathetic activity and exacerbates myocardial remodeling after myocardial infarction: evidence from an animal experiment. PLoS One 2014;9:e101734.

Pfeffer JM, Pfeffer MA, Braunwald E. Influence of chronic captopril therapy on the infarcted left ventricle of the rat.Circ Res 1985;57:84-95.

Wu RM, Jiang B, Li H, Dang WZ, Bao WL, Li HD, et al.A network pharmacology approach to discover action mechanisms of Yangxinshi Tablet for improving energy metabolism in chronic ischemic heart failure. J Ethnopharmacol 2020;246:112227.

Grønli J, Murison R, Fiske E, Bjorvatn B, Sørensen E,Portas CM, et al. Effects of chronic mild stress on sexual behavior, locomotor activity and consumption of sucrose and saccharine solutions. Physiol Behav 2005;84:571-577.

Aronsen JM, Espe EKS, Skardal K, Hasic A, Zhang L,Sjaastad I. Noninvasive stratification of postinfarction rats based on the degree of cardiac dysfunction using magnetic resonance imaging and echocardiography. Am J Physiol Heart Circ Physiol 2017;312:H932-H942.

Porsolt RD, Pichon ML, Jalfre M. Depression: a new animal model sensitive to antidepressant treatments. Nature 1977;266:730-732.

Wang Y, Liu J, Ma A, Chen Y. Cardioprotective effect of berberine against myocardial ischemia/reperfusion injury via attenuating mitochondrial dysfunction and apoptosis. Int J Clin Exp Med 2015;8:14513-14519.

Lin S, Chu JF, Zhang L, Chen DX, Xiao F, Chen HW,et al. Protective effects of Shexiang Tongxin Dropping Pill on pituitrininduced acute myocardial ischemia in rats. Mol Med Rep 2017;16:3125-3132.

Huffman JC. Review: depression after myocardial infarction is associated with increased risk of all-cause mortality and cardiovascular events. Evid Based Ment Health 2013;16:110.

Kim YH, Kim SH, Lim SY, Cho GY, Baik IK, Lim HE,et al. Relationship between depression and subclinical left ventricular changes in the general population. Heart 2012;98:1378-1383.

van Melle JP, de Jonge P, Ormel J, Crijns HJGM, van Veldhuisen DJ, Honig A, et al. Relationship between left ventricular dysfunction and depression following myocardial infarction: data from the MIND-IT. Eur Heart J 2005;26:2650-2656.

Nakatani S. Echocardiography. Nihon Rinsho 2006;64:867-873.

de Silva M, Mihailovic A, Toaldo MB. Two-dimensional,M-mode, and Doppler echocardiography in 22 conscious and apparently healthy pet guinea pigs. J Vet Cardiol 2020;27:54-61.

Lee B, Choi GM, Sur B. Antidepressant-like effects of hesperidin in animal model of post-traumatic stress disorder. Chin J Integr Med 2021;27:39-46.

Hirschfeld RM. History and evolution of the monoamine hypothesis of depression. J Clin Psychiatry 2000;61(Suppl 6):4-6.

Maddison DC, Giorgini F. The kynurenine pathway and neurodegenerative disease. Semin Cell Dev Biol 2015;40:134-141.

Campbell BM, Charych E, Lee AW, Moller T. Kynurenines in CNS disease: regulation by inflammatory cytokines. Front Neurosci 2014;8:12.

Zunszain PA, Anacker C, Cattaneo A, Choudhury S,Musaelyan K, Myint AM, et al. Interleukin-1beta: a new regulator of the kynurenine pathway affecting human hippocampal neurogenesis. Neuropsychopharmacology 2012;37:939-949.

Connor TJ, Starr N, O'sullivan JB, Harkin A. Induction of indolamine 2,3-dioxygenase and kynurenine 3-monooxygenase in rat brain following a systemic inflammatory challenge: a role for IFN-gamma? Neurosci Lett 2008;441:29-34.

Molteni R, Macchi F, Zecchillo C, Dell'agli M, Colombo E,Calabrese F, et al. Modulation of the inflammatory response in rats chronically treated with the antidepressant agomelatine.Eur Neuropsychopharmacol 2013;23:1645-1655.

Siricilla S. High-throughput assay development for combined in vitro toxicity screening of hit compounds and their metabolites in early drug-discovery stage. Bioanalysis 2017;9:959-961.

Janzen WP. Screening technologies for small molecule discovery: the state of the art. Chem Biol 2014;21:1162-1170.

More>

浏览量

Downloads

CSCD

文章被引用时，请邮件提醒。

Submit

工具集

关联资源

Meranzin Hydrate Improves Depression-Like Behaviors and Hypomotility via Ghrelin and Neurocircuitry

Efficacy and Safety of Jianpi Jieyu Decoction for Patients with Mild-to-Moderate Depression of Xin (Heart)-Pi (Spleen) Deficiency Syndrome: A Multi-centre Randomized Controlled Study

Effect of Interactive Dynamic Scalp Acupuncture on Post-Stroke Cognitive Function, Depression, and Anxiety:A Multicenter, Randomized, Controlled Trial

Antidepressant-Like Effects of Chaihu Shugan Powder(柴胡疏肝散) on Rats Exposed to Chronic Unpredictable Mild Stress through Inhibition of Endoplasmic Reticulum Stress-Induced Apoptosis*

Mechanism of Chaihu Shugan Powder (柴胡疏肝散) for Treating Depression Based on Network Pharmacology