Protective effects of ischemic preconditioning on liver injury induced by hepatic ischemia-reperfusion in rats

ObjectiveTo investigate the molecular mechanism of classic ischemic preconditioning (IPC) to induce ischemic tolerance. MethodsAfter the models of sham-operation and partial hepatic ischemia were established in rats, IPC was performed with a 10-min ischemia followed by a 10-min reperfusion. ResultsA significant increase in adenosine and NO production was found immediately after the hepatic IPC as compared with the control group (P0.01). This increase in NO content was markedly prevented by the administration of adenosine A_2 receptor antagonist to the IPC group (P0.01). An obvious decrease in release of TNF-a and an increase in production of IL-10 were found in IPC group at the 2nd h after reperfusion (P0.01). The levels of AST, ALT, LDH and W/D were significantly lower in IPC group than in I/R group (P0.01). The values of these parameters were remarkably decreased by administration of adenosine in the I/R group (P0.01). Pretreatment with adenosine A_1 receptor antagonist resulted in increase of TNF-a, AST, ALT, LDH and W/D levels but decrease of IL-10. However, pretreatment with adenosine A_2 receptor antagonist and NAME abolished the protective effects of IPC. The administration of NO precursor to the IPC+A_2 antagonist group prevented the injurious effect of A_2 receptor antagonist on hepatic IPC, leading to the same results as those observed in the IPC group. ConclusionsAn elevated adenosine extracellular concentration induces the activation of adenosine A_2 receptor, which, in turn, by induction of NO synthesis and subsequent prevention of TNF-a liberation and promotion of IL-10 production, confers cytoprotection to ischemic tissue.