Effect of Sevoflurane Post-conditioning on AKT/mTOR Pathway for Protecting Cardiac Ischemia/reperfusion Injury in Isolated Rat’s Heart / 中国循环杂志

ABSTRACT

Objective: To investigate the effect of sevolfurane (SEVO) post-conditioning on protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway for protecting ischemia/reperfusion (I/R) injury in isolated rat’s heart. Methods: A total of 84 isolated rat’s heart prepared by Langendorff method were randomly divided into 7 groups andn=12 in each group.①Sham group,②I/R group,③SEVO post- conditioning (SPC) group,④NVP-BEZ235 solvent dimenthyl sulfoxide (DMSO) group,⑤Phosphatidyl inositol 3-kinase (PI3K)/mTOR dual inhibitor NVP-BEZ235 (BEZ) group,⑥BEZ+SPC group and⑦SEVO alone group. The hearts received 30 min ischemia followed by 120 min reperfusion with relevant treatment except for Sham group and SEVO group in which the hearts were without ischemia process. Myocardial infarct (MI) size and tissue pathological changes were observed, protein expressions of phosphor-AKT (P-AKT)/total-AKT, P-mTOR/total-mTOR, Beclin1, Bax/Bcl-2 and cleaved Caspase-3 were examined at the end of reperfusion respectively. Results: Compared with I/R group, SPC group presented decreased MI size (26.28±4.00) % vs (49.22±3.66) % and reduced tissue pathological changes; up-regulated protein expressions of P-AKT/total-AKT and P-mTOR/total-mTOR by 79.85% and 67.02%, while down-regulated protein expressions of Beclin1, Bax/Bcl-2 and cleaved Caspase-3 by 33.77%, 69.26% and 48.84%respectively, allP<0.05. Compared with SPC group, BEZ+SPC group sowed increased MI size (53.85±4.06) % vs (26.28±4.00) %and elevated tissue pathological changes; down-regulated proteins expressions of P-AKT/total-AKT and P-mTOR/total-mTOR by 46.06% and 42.95%, while up-regulated protein expressions of Beclin1, Bax/Bcl-2 and cleaved Caspase-3 by 29.90%, 206.85% and 114.65% respectively, allP<0.05. Conclusion: SPC may activate AKT/mTOR pathway and inhibit cardiomyocyte autophagy and apoptosis, thereby attenuate I/R injury in isolated rats’ heart.