关键词: 再灌注损伤, 缺血预处理, 自噬

Abstract: Objective To explore the neuroprotective mechanism of autophagy involved in cerebral ischemic preconditioning. 
Methods The model of cerebral ischemia and reperfusion in rats was made by the thread plug method. A total of 100 adult SD rats were randomly divided into sham operation group(group A), ischemia-reperfusion group(group B), ischemic preconditioning group(group C), ischemia-reperfusion+autophagy inhibitor 3-Methyladenine(3-MA) group(group D), and ischemic preconditioning+3-MA group(groupE). The rats in groups D and E were injected with 3-MA(7.5 μg) into the lateral ventricle, and the rats in the other three groups were injected with the same volume of normal saline. The cerebral infarction volume, neurological deficit score, autophagy system expression level and neuronal apoptosis in each group were observed. 
Results The scores of cerebral infarction volume and neurological dysfunction in group A were both 0; the cerebral infarction volume and neurological dysfunction scores of group C were smaller or lower than those of group B; the cerebral infarction volume and neurological dysfunction scores of group D were greater than those of group B and smaller than those of group C; cerebral infarction volume and neurological dysfunction scores in group E were greater than those of group C and smaller than those of group D, suggesting significant difference(P＞0.05). Observation of neurons under an optical microscope showed that a large number of neurons and complete morphology in group A; the remaining four groups had a small number, with morphological damage, rupture and pyknosis of the nucleus, the most serious of which were group B and C. The number of neurons in group D and E was more than that in group B and C, and cell edema and nuclear damage were less. There was less expression of Beclin-1, LC3-Ⅱ and TUNEL staining-positive cells in group A, while Beclin-1, LC3-Ⅱ and TUNEL staining-positive cells in the remaining 4 groups had more expression. The number of Beclin-1, LC3-Ⅱ positive cells in group C was greater than that of group B, and the number of TUNEL staining-positive cells was less than that of group B; the number of Beclin-1, LC3-Ⅱ positive cells and the number of TUNEL staining-positive cells in group D were less than those of group B and C. The number of TUNEL staining-positive cells was greater than that of groups B and C; the number of Beclin-1 and LC3-Ⅱ positive cells in group E was less than that of group C, and the number of TUNEL staining-positive cells was less than that of group D, suggesting significant difference(P＜0.05). 
Conclusion After ischemic preconditioning, the ability of cell autophagy is strengthened, inhibiting neuronal apoptosis, and protecting intracranial neurons after ischemia-reperfusion. 

Key words: reperfusion injury； ischemic preconditioning； autophagy