摘要：Stroke remains one of the leading causes of permanent disability and death worldwide. Apoptosis and autophagy are two key elements involved in ischemic brain damage. Ethanol is a commonly used and abused chemical substance that affects the prognosis of ischemic stroke. We determined the influence of chronic ethanol consumption on apoptosis and autophagy following transient focal cerebral ischemia. Male C57BL/6 J mice were randomly divided into three groups and gavage fed with 0.7 and 2.8 g/kg/day ethanol or volume-matched water daily for 8 weeks. DNA fragmentation, TUNEL-positive neurons, cleaved caspase-3-positive neurons, translocation of mitochondrial cytochrome C and apoptosis inducing factor (AIF), LC3B-positive neurons, and expression of LC3B, Beclin-1 and Bcl-2 in peri-infarct cortex were evaluated at 24 hours of reperfusion after a 90-minute unilateral middle cerebral artery occlusion (MCAO). Cerebral ischemia/reperfusion (I/R) injury was significantly improved in the 0.7 g/kg/d ethanol group but worsened in the 2.8 g/kg/d ethanol group. DNA fragmentation was significantly increased at 24 hours of reperfusion in all groups. However, the magnitude of the increase was significantly less in the 0.7 g/kg/d ethanol group. In addition, both cleaved caspase-3-positive neurons and TUNEL-positive neurons were significantly less in 0.7 g/kg/d ethanol group. Furthermore, translocation of mitochondrial cytochrome C and AIF was significantly alleviated in the 0.7 g/kg/d ethanol group. On the other hand, baseline expression of LC3B was significantly reduced in the 2.8 g/kg/d ethanol group. Post-ischemic expression of LC3B and LC3B-positive neurons were significantly attenuated in both 0.7 and 2.8 g/kg/d ethanol groups. Moreover, although post-ischemic expression of Beclin-1 was not altered in the ethanol groups, post-ischemic expression of Bcl-2 was significantly greater in both 0.7 and 2.8 g/kg/d ethanol groups. Our findings suggest that light ethanol consumption may protect against cerebral I/R injury by suppressing post-ischemic apoptosis, whereas heavy ethanol consumption may exacerbate cerebral I/R injury by suppressing autophagy.
