OBJECTIVE:To investigate whether peroxisome proliferator-activated receptor γ-coactivator-1α/nuclear respiratory factor 1(PGC-1α/NRF1)activity can protect mitochondrial function in the setting of cardiac hypertrophy and improve cardiomyocyte energy metabolism.METHODS:Cardiac hypertrophy was modeled in H9c2 cells treated with isoproterenol(ISO)to assess the effects of Shenge San(参蛤散,SGS)on cell viability and mitochondrial membrane potential.We assessed mitochondrial complex mRNA levels and mitochondrial oxidative phosphorylation factor mRNA and protein levels.RESULTS:Compared with the 100 μM ISO group,cell size was significantly decreased in the 0.3 mg/mL SGS and 20 μM ZLN005(PGC-1α activator)groups(P＜0.01).Compared with the SGS(0.3)+ISO group,we observed lower phosphorylated adenosine monophosphate-activated kinase(AMPK)protein levels in the ISO and ZLN005+SGS+ISO groups(P＜0.01).Compared with the compound C group,SGS significantly increased PGC-1αexpression in ISO-induced cardiac hypertrophy cells(P＜0.01),and this was inhibited by compound C pretreatment(P＜0.05).Compared with the ISO group,the mitochondrial red-green fluorescence ratio increased in the 0.3 mg/mL SGS group(P＜0.05).mRNA levels of cytochrome c oxidase subunit 1(CO1)in the ISO and compound C groups were lower than those in control group(P＜0.01),and the mRNA levels of CO1 and ATP8 were significantly lower in the ISO and compound C groups versus control(P＜0.01).Compared with the SGS(0.3)+ISO group,ATP synthetase subunit 8(ATP8)mRNA was significantly decreased in the ISO group(P＜0.01)and compound C+SGS+ISO group(P＜0.05).Compared with the SGS(0.3)+ISO group,NRF1 mRNA levels were significantly decreased(P＜0.05)in the ISO and compound C+SGS+ISO groups.CONCLUSIONS:SGS can attenuate ISO-induced cardiomyocyte hypertrophy,restore the decrease in mitochondrial membrane potential,and upregulate PGC-1α/NRF1 levels.Notably,these effects can be blocked by AMPK inhibitor-compound C.

ZHU Lingyan;WEI Yihong;WANG Youhua;YANG Jianmei;LI Jiawei;CAO Min;ZHOU Duan

Department of Traditional Chinese Medicine,Shanghai Xuhui Central Hospital,Shanghai 200031,China;Cardiovascular Research Center,Longhua Hospital Shanghai University of Traditional Chinese Medicine,Shanghai 200032,China;Kangjian Community Health Service Centre,Shanghai 200233,China;Emergency department,Longhua Hospital Shanghai University of Traditional Chinese Medicine,Shanghai 200032,China

中医杂志（英文版）

[1]ZHU Lingyan;WEI Yihong;WANG Youhua;YANG Jianmei;LI Jiawei;CAO Min;ZHOU Duan-.Protective efficacy of Shenge San(参蛤散)on mitochondria in H9c2 cardiomyocytes)[J].中医杂志（英文版）,2022(06):892-899

Shenge,参蛤散,ZLN005,+ISO,ZLN005+SGS+ISO,C+SGS+ISO

Protective,efficacy,San,H9c2,cardiomyocytes,OBJECTIVE,To,investigate,whether,peroxisome,proliferator,activated,receptor,coactivator,nuclear,respiratory,PGC,NRF1,activity,protect,mitochondrial,function,setting,cardiac,hypertrophy,improve,energy,metabolism,METHODS,Cardiac,was,modeled,cells,treated,isoproterenol,effects,viability,membrane,potential,We,assessed,complex,levels,oxidative,phosphorylation,protein,RESULTS,Compared,size,significantly,decreased,groups,observed,lower,phosphorylated,adenosine,monophosphate,kinase,AMPK,compound,increased,expression,induced,this,inhibited,by,pretreatment,green,fluorescence,ratio,cytochrome,oxidase,subunit,CO1,were,than,those,control,ATP8,versus,synthetase,CONCLUSIONS,attenuate,restore,upregulate,Notably,these,be,blocked,inhibitor

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