Effects of autophagy on acute kidney injury after liver transplantation

Abstract

Objective To evaluate the role of autophagy on acute kidney injury after liver transplantation. Method Fifty-six healthy male Sprague-Dawley rats were randomly assigned into 4 groups: sham group, orthotopic liver transplantation (OLT) group, sirolimus pretreated (SRL) group and 3-methyladenine pretreated (3-MA) group. OLT model was established. Then the rats were sacrificed at 6 h after reperfusion. The renal function and the extent of oxidative stress relative proteins malondialdehyde (MDA) and superoxide dismutase (SOD) were observed. The levels of apoptosis relative genes caspase-3 and cyt c and the expression of autophagy relative proteins were detected. The pathological changes were microscopically examined in renal tissues. TUNEL staining was used to observe the apoptosis of tubular epithelial cells. Transmission electron microscopy was applied to observe the ultrastructure changes of tubular epithelial cells. Result As compared with sham group, OLT and 3-MA groups showed a serious renal injury including cellular vacuolization, loss of brush borders, and a significant rise in BUN, Cr and MDA, while a decrease in SOD activity. The levels of caspase-3 mRNA and cyt c mRNA were increased significantly. Whereas compared to OLT and 3-MA groups, renal function and oxidative stress levels in SRL group ameliorated, and histopathologic damage and apoptosis alleviated after OLT. Simultaneously, the levels of caspase-3 mRNA and cyt c mRNA were decreased. The expression of beclin-1 and LC3-Ⅱ was effectively up-regulated. Conclusion Autophagy could alleviate acute kidney injury after liver transplantation through inhibiting oxidative stress and apoptosis. Key words: Rats; Liver transplantation; Kidney injury; Autophagy