Enhanced autophagy alleviates injury during hindlimb ischemia/reperfusion in mice.

Previous studies examining whether autophagy has a protective or deleterious role during ischemia/reperfusion (I/R) injury have reported a varying role in different organs and remains a matter of debate. The aim of the current study was to explore the role of autophagy in hindlimb I/R injury in a murine model. An increase in apoptosis was observed in vitro, in C2C12 myoblast cells, following hypoxia/reoxygenation (H/R), while downregulation of autophagic flux was induced by chloroquine as compared with the vehicle group under hypoxia and H/R conditions. In vivo, an increase in severe damage of gastrocnemius muscles was observed in the I/R and ischemia groups compared with the control group, was more severe in the I/R group compared with the ischemia group. Electron microscopy revealed an increased number of autophagosomes in the ischemia group, whereas a reduced number was detected in the I/R group. Following administration of rapamycin, the infarct size ratio and cell apoptosis was significantly reduced, while the amount of autophagosomes significantly increased in the ischemic phase. In conclusion, autophagy is upregulated in the ischemia phase and downregulated in the reperfusion phase. Notably, upregulation of autophagy via rapamycin intervention during ischemia alleviated skeletal muscle damage, suggesting a potential protective role during hindlimb I/R injury.