The Influence Of Ischemic Preconditioning On Liver Regeneration As Well As The Effects Of IL-6 And TNF-α In Partial Hepatectomy Rats

Objectives:This study was undertaken to confirm that IPC has a sign- ifycant impact on liver regeneration of hepatocytes after partial hepatic- tomy in ischemically damaged liver.In addition,we sought to examine the role of tumor necrosis factor-αand interleukin-6 in this process.Methods:Male Sprague-Dawley rats were subjected to 30 min of partial hepatic ischemia,and 70%hepatectomy was performed just before reperfusion.Animals were pre-treated with either IPC(5/10 min)(IPC +PH group)or not(ischemia +PH).The survival rate,serum transaminases, tumor necrosis factorα(TNF-α),and interleukin-6(IL-6)levels,hepatocyte proliferation and histological change of the remnant liver were measured in both groups and compared with non-ischemic controls subjected to 70% hepatectomy alone(PH group).Results:The survival rate was significantly better in the IPC +PHx group than in the ischemia +PHx group. Furthermore,IPC reduced liver injury determined by liver histology and serum transaminases.There was an early rise in serum TNF-αand IL-6 levels in the ischemia+ PHx group.Compared with non-ischemic controls, IPC significantly decreased TNF-α,but not IL-6 during the late(24 and 48 h)phases of reperfusion.Rats subjected to 70%hepatectomy and 30 min of hepatic ischemia showed signifycantly reduced hepatocyte proliferation (mitotic index,proliferating cell nuclear antigen,and relative liver weight) when compared with animals subjected to hepatectomy alone.However, hepatocyte proliferation was markedly increased in rats pretreatment with IPC when compared with ischemic controls.Conclusions:These results suggest that ischemic preconditioning ameliorates the hepatic injury associated with ischemia-reperfusion and has a stimulatory effect on liver cell regeneration that may make it valuable as a hepatoprotective modality. Il-6 appears to be key mediator in promoting regeneration after combined ischemia and hepatic resection.