Sodium hydrosulfide attenuates cerebral ischemia/reperfusion injury by suppressing overactivated autophagy in rats

Abstract

Ischemic stroke is a leading cause of death and disability worldwide, and autophagy may be involved in the pathological process of cerebral ischemia/reperfusion injury. Hydrogen sulfide (H 2 S) is an endogenous gasotransmitter with protective effects against multiple diseases. Here, we tested the effect of H 2 S on cerebral ischemia/reperfusion injury in rats. Sodium hydrosulfide (Na HS ), an H 2 S donor, improved neurological function and reduced the size of the infarcts induced by transient middle cerebral artery occlusion ( MCAO ) followed by reperfusion in rats. Na HS treatment reduced the lactate dehydrogenase ( LDH ) activity in the serum (a marker of cellular membrane integrity) and the expression of cleaved caspase‐3 (a marker for apoptosis) in the brains of MCAO rats. We also found that autophagy was overactivated in the brains of MCAO rats, as indicated by an increased ratio of LC 3 II to I, decreased expression of p62, and transmission electron microscope detection. Na HS treatment significantly inhibited the autophagic activity in the brains of MCAO rats. Furthermore, PC 12 cells were subjected to oxygen–glucose deprivation/reoxygenation ( OGD /R) to mimic MCAO in vitro . We found that Na HS treatment reduced cellular injury and suppressed overactivated autophagy induced by OGD /R in PC 12 cells. An autophagy stimulator (rapamycin) eliminated the protective effect of Na HS against LDH release and caspase‐3 activity induced by OGD /R in PC 12 cells. An autophagy inhibitor (3‐methyladenine, 3‐ MA ) also reduced the cellular injury induced by OGD /R in PC 12 cells. In conclusion, the results indicate that overactivated autophagy accelerates cellular injury after MCAO in rats and that exogenous H 2 S attenuates cerebral ischemia/reperfusion injury via suppressing overactivated autophagy in rats.