Ischemia-reperfusion injury induces autophagy inhibition in aged rats / 中华器官移植杂志

ABSTRACT

Objective To explore the mechanism of hepatic autophagy inhibition induced by ischemia-reperfusion injury in the aging liver.Methods The healthy male Lewis rats aged 3 months (3M) and 24 months (24M) were selected,and then were randomly divided into 3M IRI group,3M sham operation group,24M IRI group,24M sham operation group.In the experimental group,noninvasive vascular clamp was used to clamp the left and middle hepatic lobes (about 70o％ hepatic ischemia).The liver was subjected to ischemia at 37 0.5℃ for 30min and reperfusion for 6h.The hepatic duodenal ligament was dissected only by sham operation.The serum levels of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured at 6 h after operation.Liver tissues of each group were examined by liver pathology and the number of autophagosome of LC3B in liver tissue of each group was observed under confocal microscopy.The changes of autophagyrelated protein were analyzed by Western blotting.Results The levels of serum ALT and AST in 24M IRI group were significantly higher than those in 3M IRI group,the difference was statistically significant (P＜0.05).Pathological analysis showed that 3M IRI group showed spotty necrosis,the 24M IRI group showed massive necrosis and the infiltration of the inflammatory cells;Confocal microscopy showed that the number of autophagosome in the liver tissue of the 24M sham group was slightly lower than that of the 3M sham operation group and the number of autophagosome in the 24M IRI group was significantly lower than that in the 3M IRI group (P＜0.05).The levels of autophagyrelated proteins (Beclin1 and ATG4B protein) in 24M IRI group were significantly down-regulated compare to 3M IRI group (P＜0.05).Conclusion The ischemia-reperfusion injury of liver in aged rats inhibits autophagy,and its mechanism may be related to the decrease of autophagy-related protein level in hepatic ischemia-reperfusion injury.