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-1 β,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(P＜0.01).Meanwhile,YXNS effectively reduced MI size and cardiomyocytes apoptosis of rats(P＜0.01 or P＜0.05),promoted AMPK phosphorylation,and increased PGC-1α protein expression(P＜0.01 or P＜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,NE,ACTH,and CORT(all P＜0.05).Moreover,HYXNS decreased the mRNA expressions of IDO1,KMO and KYNU(P＜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.

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

Department of Pharmacology,School of Pharmacy,Fudan University,Shanghai,200120,China;Department of Pharmacology of Chinese Materia Medica,School of Traditional Chinese Medicine,Guangdong Pharmaceutical University,Guangzhou,510006,China;Central Research Institute,Shanghai Pharmaceuticals Holding Co.,Ltd.,Shanghai,200120,China

中国结合医学杂志（英文版）

[1]JIANG Bing;WU Ruo-ming;Li Hai-dong;LI Kun;LI Hui;DANG Wen-zhen;FENG Gui-ze;BAO Wei-lian;YE Guan;SHEN Xiao-yan-.Yixin Ningshen Tablet Alleviates Comorbidity of Myocardial Infarction and Depression by Enhancing Myocardial Energy Metabolism and Increasing Availability of Monoamine Neurotransmitter)[J].中国结合医学杂志（英文版）,2022(07):586-593

Yixin,Ningshen,Monoamine,Neurotransmitter,YXNS,FLXT,LYXNS,HYXNS,kynureninase,KYNU

Tablet,Alleviates,Comorbidity,Myocardial,Infarction,Depression,by,Enhancing,Energy,Metabolism,Increasing,Availability,Objective,To,investigate,therapeutic,comorbidity,myocardial,infarction,MI,depression,rats,explore,underlying,mechanism,Methods,Sprague,Dawley,were,randomly,divided,into,groups,each,according,their,weights,including,control,model,fluoxetine,low,dose,high,pretreated,corresponding,drugs,weeks,was,constructed,ligation,left,anterior,descending,coronary,artery,chronic,mild,stress,stimulation,echocardiography,sucrose,preference,test,open,field,forced,swim,performed,area,apoptosis,also,detected,Serum,levels,interleukin,tumor,necrosis,hydroxytryptamine,HT,adrenocorticotrophic,hormone,ACTH,corticosterone,CORT,norepinephrine,NE,determined,enzyme,linked,immunosorbent,assay,proteins,adenosine,monophosphate,activated,kinase,AMPK,peroxisome,proliferator,receptor,gamma,coactivator,PGC,nuclear,respiratory,NRF1,heart,blot,analysis,indoleamine,dioxygenase,IDO1,kynurenine,monooxygenase,KMO,hippocampus,real,quantitative,polymerase,chain,reaction,Results,Compared,cardiac,function,significantly,improved,Meanwhile,effectively,reduced,size,cardiomyocytes,promoted,phosphorylation,increased,locomotor,activity,decreased,serum,Moreover,expressions,Conclusions,relieve,enhancing,energy,metabolism,alleviate,resisting,inflammation,increasing,availability,monoamine,neurotransmitters,It,may,used,potential

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