Experimental study of the effects of deletion variant of hepatocyte growth factor on hepatic ischaemia-reperfusion injury.
BACKGROUND
Hepatic ischaemia-reperfusion (IR) injury is still a serious complication following liver surgery. The effect of the deletion variant of hepatocyte growth factor (dHGF) on hepatic IR injury was examined in rats.


METHODS
Male Wistar rats were divided into two groups after 90 min of partial liver ischaemia: the dHGF group which was given dHGF 0.5 mg/kg intravenously immediately after reperfusion, followed by 0.5 mg/kg every 12 h, and the control group, which received vehicle buffer only. Serum chemistry, histopathological findings and liver weights were compared between the groups.


RESULTS
In the dHGF group, the increase in serum alanine transaminase and hyaluronic acid levels was significantly reduced, and the serum albumin level increased after reperfusion. The extent of hepatic necrosis 24 h after reperfusion was decreased in the dHGF group. Moreover, the proportion of terminal deoxynucleotidyl transferase-mediated 2'-deoxyuridine 5'-triphosphate nick end labelling-positive hepatocytes 6 h after reperfusion was reduced in the dHGF group. The non-ischaemic-, ischaemic- and whole-liver weight : body-weight ratio significantly increased in the dHGF group after reperfusion. The proportion of proliferating cell nuclear antigen-positive hepatocytes in the dHGF group markedly increased after 6 h after reperfusion in the non-ischaemic lobes, while in the ischaemic lobes it increased 24 h after reperfusion.


CONCLUSIONS
These data suggest that dHGF not only improves recovery from IR injury, but also accelerates recovery from these injuries. dHGF may be an effective pharmacological agent for prevention and treatment of hepatic IR injury.
Ikegami
T
T
Department of Surgery II, Kyushu University, Fukuoka, Japan.
Nishizaki
T
T
Uchiyama
H
H
Hashimoto
K
K
Yanaga
K
K
Sugimachi
K
K
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D004353:Drug Evaluation, Preclinical; D017228:Hepatocyte Growth Factor / Q000235:genetics / Q000494:pharmacology*; D008107:Liver Diseases / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D009336:Necrosis; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000473:pathology / Q000517:prevention & control*
D017228:Hepatocyte Growth Factor