摘要
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 m RNA levels and mitochondrial oxidative phosphorylation factor m RNA and protein levels. RESULTS: Compared with the 100 μM ISO group, cell size was significantly decreased in the 0.3 mg/m L 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 monophosphateactivated 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-1α expression 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/m L SGS group(P < 0.05). m RNA 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 m RNA 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) m RNA 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 m RNA 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.
