Effect of Ischemic Preconditioning on Levels of TNF-α and IL-10 in Rat Livers After Ischemia-Reperfusion

Objective: Our aim was to investigate the molecular mechanisms of classic ischemic preconditioning(IPC) in ischemic tolerance. Methods: The models of sham-operation and partial hepatic ischemia were established in rats. The changes of levels of tumor necrosing factor (TNF-α) and interleukin-10 (IL-10) in IPC were observed. Results: Adenosine and NO production increased significantly immediately after the hepatic IPC and were higher than those in the control group (P0.01). However, the increase of NO was inhibited after the administration of adenosine A 2 receptor antagonist in the IPC group (P0.01). The TNF-α decreased and production of IL-10 increased in IPC group 2 hours after reperfusion (P0.01).The contents of AST, ALT and LDH, and the level of W/D in IPC group were lower than those in the I/R group (P0.01). All of these decreased after the administration of adenosine in the I/R group (P0.01). Pretreatment with adenosine A 1 receptor antagonist caused the results similar to the results in the IPC group, while the pretreatment with adenosine A 2 receptor antagonist and NAME made the protective effect of IPC disappeared, showing similar increase in TNF-α,AST,ALT,LDH, and W/D levels and decrease in IL-10 as observed in the I/R group. However, the administration of NO precursor in the IPC+A 2 antagonist group inhibited the injurious effect of the A 2 receptor antagonist on hepatic IPC, and caused to the same results as those observed in the IPC group. Conclusion: An elevated extracellular concentration of adenosine induces the activation of adenosine A 2 receptor, which, in turn, by induction of NO synthesis and subsequent inhibition of TNF-α and production of IL-10, confers cytoprotection to ischemic tissue.