Recent studies have shown that metformin activates AMP-activated protein kinase (AMPK) and has a potentcardioprotective effect against ischemia/reperfusion injury. Previous studies have focused on the protective effects of metformin on cardiomyocytes,and the mechanisms by which metforminexerts these cardioprotective effects remain unclear. our study aimed to investigate if metformin has beneficial effects on damaged cardiosphere-derived cellsby H2O2, and reveal the potential mechanism of action of cardioprotective effect of metformin.Methods
And Result Cardiosphere-derived cells were cultured from the ventricles of one-day-old Sprague Dawley rats, and these cells were incubated in the presence of 50 µmol/l H2O2 for 24 h. Cardiosphere-derived cellswere pretreated with metformin at different concentrations and time and with aminoimidazole carboxamide ribonucleotide (AICAR) (400 µmol/l), an adenosine monophophate (AMP)-activated protein kinase (AMPK) agonist for 60 min before the addition of H2O2. Other cells were preincubated with compound C (an AMPK antagonist, 20 μmol/l) for 4 h. The viability and apoptosis of cells were analysed by CCK8,flowcytometry,and TUNEl. AMPK and endothelial nitric oxide synthase (eNOS) were analysed using immunblotting. Metformin had antagonistic effects on the influences of H2O2 on cell viability and attenuated oxidative stress-induced apoptosis. Metformin also increased phosphorylation of AMPK and eNOS.Conclusions
Metformin attenuated oxidative stress–induced cardiosphere-derived cells apoptosis, The protectiveeffects of metformin were associated withactivation of the AMPK-eNOS pathway.