OBJECTIVE:To determine whether Shunxin decoction(顺心组方)improves diastolic function in rats with heart failure with preserved ejection fraction(HFpEF)by regulating the cyclic guanosine monophosphate-dependent protein kinase(cGMP-PKG)signaling pathway.METHODS:Except for control group 8 and sham surgery group 8,the remaining 32 male Sprague-Dawlay rats were developed into HFpEF rat models using the abdominal aorta constriction method.These rats in the HFpEF model were randomly divided into the model group,the Shunxin high-dose group,the Shunxin low-dose group,and the Qiliqiangxin capsule group.The three groups received high-dose Shunxin decoction,low-dose Shunxin decoction,and Qiliqiangxin capsule by gavage,respectively,for 14 d.After the intervention,the diastolic function of each rat was evaluated by testing E/A,heart index,hematoxylin-eosin staining,Masson,myocardial ultrastructure,and N-terminal pro-brain natriuretic peptide(NT-proBNP).The Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine(BATMAN-TCM)software was used to predict targets for which Shunxin decoction acts on the cGMP-PKG pathway.Natriuretic peptide receptor A(NPRA)and guanylate cyclase(GC)were detected by immunohistochemistry,and eNOS,phosphodiesterase 5A(PDE5A),and cGMP-dependent protein kinase 1(PKG I)were determined by Western blotting.RESULTS:Compared to the model group,the thickness of the interventricular septum at the end of diastole(IVSd)and the thickness of the posterior wall at the end of diastole(PWd)of the Shunxin decoction high-dose group,Shunxin decoction low-dose group,and Qiliqiangxin capsule group were all significantly reduced(P＜0.01).Furthermore,Shunxin decoction high-dose group E/A value was decreased(P＜0.01).Compared to the model group,the expression of NPRA and GC increased in the Shunxin decoction low-dose group and the Qiliqiangxin capsule group(P＜0.01).Compared to the model group,the expressions of eNOS and PKG I increased(P＜0.05)in the Shunxin decoction high-dose group.The expression of PDE5A expression decreased in the myocardium of the Shunxin decoction high-dose group,Shunxin decoction low-dose group,and Qiliqiangxin capsule group compared to the model group(P＜0.01).CONCLUSIONS:Shunxin decoction can improve diastolic function in rats with HFpEF.It increases the expression of NPRA,GC,and eNOS in the myocardial cell cGMP-PKG signaling pathway,upregulates cGMP expression,decreases PDE5A expression to reduce the cGMP degradation.Thus,the cGMP continually stimulates PKG I,reversing myocardial hypertrophy and improving myocardial compliance in HFpEF rats.

ZHANG Jiaying;WEI Xiangxiang;LI Xuefeng;YUAN Yang;DOU Yinghuan;SHI Yanbin;XIE Ping;ZHOU Mengru;ZHAO Junnan;LI Miao;ZHANG Shuwen;ZHU Rui;TIAN Ying;TAN Hao;TIAN Feifei

School of basic medical sciences,Institute of Integrated Chinese and Western Medicine,Lanzhou University,Lanzhou 730000,China;Department of Cardiology,Gansu Provincial hospital,Lanzhou 730000,China

中医杂志（英文版）

[1]ZHANG Jiaying;WEI Xiangxiang;LI Xuefeng;YUAN Yang;DOU Yinghuan;SHI Yanbin;XIE Ping;ZHOU Mengru;ZHAO Junnan;LI Miao;ZHANG Shuwen;ZHU Rui;TIAN Ying;TAN Hao;TIAN Feifei-.Shunxin decoction(顺心组方)improves diastolic function in rats with heart failure with preserved ejection fraction induced by abdominal aorta constriction through cyclic guanosine monophosphate-dependent protein kinase Signaling Pathway)[J].中医杂志（英文版）,2022(05):764-772

Shunxin,Dawlay,Qiliqiangxin,NPRA

decoction,顺心,组方,improves,diastolic,function,rats,heart,failure,preserved,ejection,fraction,induced,by,abdominal,aorta,constriction,through,cyclic,guanosine,monophosphate,dependent,protein,kinase,Signaling,Pathway,OBJECTIVE,whether,HFpEF,regulating,cGMP,PKG,signaling,pathway,METHODS,Except,control,sham,surgery,remaining,male,Sprague,were,developed,into,models,using,method,These,randomly,divided,high,dose,low,capsule,three,groups,received,gavage,respectively,After,intervention,each,was,evaluated,testing,hematoxylin,eosin,staining,Masson,myocardial,ultrastructure,terminal,brain,natriuretic,peptide,NT,proBNP,Bioinformatics,Analysis,Tool,Molecular,Mechanism,Traditional,Chinese,Medicine,BATMAN,TCM,software,used,predict,targets,which,acts,Natriuretic,receptor,guanylate,cyclase,detected,immunohistochemistry,eNOS,phosphodiesterase,PDE5A,determined,blotting,RESULTS,Compared,thickness,interventricular,septum,diastole,IVSd,posterior,wall,PWd,significantly,reduced,Furthermore,value,decreased,increased,expressions,myocardium,compared,CONCLUSIONS,It,increases,cell,upregulates,decreases,degradation,Thus,continually,stimulates,reversing,hypertrophy,improving,compliance

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