Gsk-3 Beta Mediates Ischemia-Reperfusion Injury By Regulating Autophagy In Dcd Liver Allografts

To elucidate the role of autophagy in ischemia-reperfusion injury (IRI) and determine whether glycogen synthase kinase-3 beta (GSK-3) plays an important role in autophagy, a donors of cardiac death (DCD) liver transplantation model was established to observe the expression of GSK-3 beta and autophagy in hepatocytes during liver IRI. Immunohistochemical staining and western blotting were used to detect expression of the autophagy markers, LC3 and p62, as well as study the expression of GSK-3 beta and AMPK. Serum enzymology changes were analyzed at different times after liver transplantation. Hypoxia-reoxygenation methods were used to mimic the process of ischemia-reperfusion injury in cultured hepatocytes. In DCD liver transplantation with a prolonged reperfusion time, LC3 expression increased, whereas p62 decreased. GSK-3 beta and AMPK expression in the transplanted liver tissue were consistent with changes in autophagy, ALT, and AST. In summary, inactive GSK-3 beta reduced liver IRI, promoted hepatocyte autophagy, and improved hepatocyte activity. Therefore, GSK-3 beta may regulate autophagy through the AMPK-mTOR pathway.