Excessive autophagy induced by reperfusion is one of the causes of severe myocardial injury. Tanshinone IIA (TSN) protects the myocardium against ischemia/reperfusion (I/R) injury. The mechanism by which the inhibition of excessive autophagy contributes to the myocardial protection by TSN is unclear. The protective effects and mechanisms of TSN were studied in H9c2 cells and rats after anoxia/reoxygenation (A/R)-or I/R-induced myocardial injury. The results showed that after the injury, cell viability decreased, lactate dehydrogenase and caspase 3 activity and apoptosis increased, and autophagy was excessively activated. Further, redox imbalance and energy stress, mitochondrial dysfunction, reduced myocardial function, increased infarct area, and severely damaged morphology were observed in rats. TSN increased 14-3-3η expression and regulated Akt/Beclin1 pathway, inhibited excessive autophagy, and significantly reversed the functional, enzymological and morphological indexes in vivo and in vitro. However, the protective effects of TSN were mimicked by 3-methyladenine (an autophagy inhibitor) and were attenuated by pAD/14-3-3η-shRNA, API-2 (an Akt inhibitor), and rapamycin (an autophagy activator). In conclusion, TSN could increase 14-3-3η expression and regulate Akt/Beclin1 pathway, inhibit excessive autophagy, maintain the mitochondrial function, improve energy supply and redox equilibrium, alleviate apoptosis, and ultimately protect myocardium against I/R injury.
Keywords: 14-3-3η; Akt/Beclin1 pathway; Autophagy; Ischemia/reperfusion injury; Myocardium; Tanshinone IIA.
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