Isorhynchophylline attenuates angiotensin Ⅱ-induced cardiomyocyte hypertrophy by inhibiting the Akt pathway
Objective To investigate the effect and mechanism of isorhynchophylline(IRN)on angiotensin Ⅱ(Ang Ⅱ)-induced cardiac hypertrophy.Methods H9c2 cells were co-cultured with Ang Ⅱ and different concentrations of IRN(0,5,10,25,50 μmol/L).The cell surface area and mRNA levels of cardiac hypertrophy markers atrial natriuretic peptide(ANP),brain natriuretic peptide(BNP)and β-myosin heavy chain(β-MHC)were detected to elucidate the effect of IRN on myocardial hypertrophy and the most effective concentration.H9c2 cells were co-cultured with Ang Ⅱ and IRN(25 μmol/L)at different times(0,6,12,24 h)to elucidate the most effective time of inhibition.The phosphorylation levels of the signaling pathway were detected,and the effects of IRN and Akt inhibitor MK2206 on the phosphorylation levels of the signaling pathway were further explored to elucidate the underlying mechanisms.Results Compared with the control group,the surface area of H9c2 cells,and the mRNA expression of myocardial hypertrophy markers ANP,BNP and β-MHC were significantly increased(all P＜0.05).Pretreated with different concentrations of IRN(5,10,25,50 μmol/L)could inhibit the increase in cell surface area induced by Ang Ⅱ(all P＜0.05),especially at the concentration of 25 μmol/L(P＜0.01).IRN could time-dependently inhibit Ang Ⅱ-induced activation of ANP,BNP,β-MHC mRNA(all P＜0.05).Ang Ⅱ caused increased phosphorylation levels of Akt,GSK3β,mTOR and FOXO3a.IRN could block Ang Ⅱ-induced phosphorylation of the Akt signaling pathway.Conclusion IRN attenuates Ang Ⅱ-induced cardiomyocyte hypertrophy by inhibiting the Akt signaling pathway.
万方数据
维普
