Effects of ischemic preconditioning on regenerative capacity of hepatocyte in the ischemically damaged rat livers.
BACKGROUND
Liver regeneration after partial hepatectomy is regulated by several factors that activate or inhibit hepatocyte proliferation. A short period of ischemia-reperfusion (IR), called ischemic preconditioning (IPC), protects the liver against subsequent sustained ischemic insults. The present study investigated the effects of IPC on liver regeneration after partial hepatectomy under IR in rats.


METHODS
Male Wistar rats were subjected to 45 min of total hepatic ischemia, and 70% hepatectomy was performed just before reperfusion. Animals were pre-treated with either IPC (10/15 min) (IPC + PHx group) or not (ischemia + PHx). The survival rate, serum transaminases, tumor necrosis factor (TNF)-alpha, and interleukin (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 (PHx 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-alpha and IL-6 levels in the ischemia + PHx group. Compared with non-ischemic controls, IPC significantly decreased TNF-alpha, but not IL-6 during the late (24 and 48 h) phases of reperfusion. Rats subjected to 70% hepatectomy and 45 min of hepatic ischemia showed significantly 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 pre-conditioning 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.
Bedirli
Abdulkadir
A
Department of General Surgery, University of Gazi, School of Medicine, Ankara, Turkey. bedirlia@gazi.edu.tr
Kerem
Mustafa
M
Pasaoglu
Hatice
H
Erdem
Ozlem
O
Ofluoglu
Ebru
E
Sakrak
Omer
O
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D022781:Hepatocytes / Q000502:physiology*; D015850:Interleukin-6 / Q000096:biosynthesis; D007511:Ischemia / Q000503:physiopathology*; D019194:Ischemic Preconditioning; D008099:Liver / Q000098:blood supply*; D008115:Liver Regeneration; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase