Ischemic preconditioning improves hepatic regeneration with reduced injury following reduced-size rat liver transplantation / 中国组织工程研究

ABSTRACT

BACKGROUND: Recently,liver transplantation technique has been developed rapidly,and prevention of ischemia/reperfusion injury and protection of liver regeneration have become a research focus.Ischemic preconditioning(IPC)is an effective method for protecting liver ischemic injury.However,the mechanism remains controversial.OBJECTIVE: To investigate the mechanism of IPC on hepatic injury and regeneration after reduced-size rat liver transplantation.METHODS: Animals were randomly divided into 3 groups.Rat reduced-size liver transplantation model was established in liver transplantation group.IPC+liver transplantation group underwent first porta hepatis blocking for 10 minutes before liver graft reperfusion,followed by reperfusion for 15 minutes.The ligament around the liver was dissociated in the sham-surgery group.The samples were collected 0.5,2,6 and 24 hours post-operation.The hepatic injury was examined by the serum alanine aminotransferase(ALT)and hepatic tissue histopathology analysis of grafts.Semi-quantitative immunohistochemistry and westernblotting were used to examine the redox factor-1(Ref-1)protein expression.The hepatic regeneration of the grafts was examined by the expression of proliferating cell nuclear antigen(PCNA)in hepatic cells.RESULTS AND CONCLUSION: Compared with liver transplantation group,the ALT values at 6 and 24 hours after operation in IPC group decreased significantly(P < 0.05; P < 0.01).Pathological analysis indicated that there were lots of inflammation cells around the portal veins,the serious sinus hepaticus dilation and damage of hepatic tissue in liver transplantation group.However,the tissue injury observed in IPC group was comparatively slight.Semi-quantitative immunohistochemistry revealed that Ref-1 protein was more abundant in IPC grafts tissue compared to liver transplantation group.These observations were supported by westernblotting studies where Ref-1 protein was shown to be over-expressed in IPC specimens at 24 hours after reduced-size liver transplantation(P < 0.05).In addition,the number of PCNA-positive cells in IPC group was more than liver transplantation group at 2,6 and 24 hours after operation(P < 0.05).IPC improves hepatic regeneration and relieves grafts injury in earlier period after reduced-size rat liver transplantation,which is associated with the over-expression of Ref-1protein.