Role of autophagy via PI3K/Akt signaling pathway in attenuation of doxorubicin-induced cardiomyopathy by Sevoflurane postconditioning

Objective To investigate the effect of Sevoflurane postconditioning on PI3K/Akt signaling pathway and autophagy after doxorubicin-induced cardiomyopathy. Methods The H9c2 cardiomyocytes were randomly divided into 6groups (n=6):control group (group C),Doxorubicin group (group Dox),Sevoflurane group (group Sev),LY294002group (group LY),Solvent control group (group DMSO),3-MA group (group 3-MA).In addition to the group C,the other5 groups were all established doxorubicin-induced damage to cardiomyocytes model.Group C and group Dox did not receive any treatment,group Sev,group LY (LY294002 was added to the medium before expose),group DMSO (added DMSO),group 3-MA (added 3-MA) exposed to 2.4% Sevoflurane for 2 h.The concentrations of c Tn I and Caspase-3 in the culture medium was detected by ELISA;the expression of LC3-Ⅱ,total Akt (t-Akt) and phosphorylated Akt (p-Akt) was detected by Western blot.The quantitative data were presented as mean±standard deviation (x±s).The groups were compared using ANOVA. Results Compared with group C,the p-Akt expression was decreased,LC3-Ⅱ expression,apoptosis index,serum c Tn I and Caspase-3 concentration were significantly increased in the other five groups (P<0.05).Compared with group Dox,expression of p-Akt was increased,the expression of LC3-Ⅱ,apoptosis index,c Tn I and Caspase-3 were decreased in group Sev (P<0.05).Compared with group Sev,p-Akt was decreased,the expression of LC3-Ⅱ,apoptosis index,serum c Tn I and Caspase-3 concentration were increased in group LY (P<0.05);the expression of LC3-Ⅱ,c Tn I and Caspase-3 were decreased in group 3-MA (P<0.05). Conclusion Sevoflurane postconditioning on cardiomyocytes may reduce the myocardial cell injury induced by adriamycin,which may be related to the activation of PI3 K/Akt pathway to inhibit the excessive activation of autophagy.