Deletion variant of hepatocyte growth factor prolongs allograft survival after liver transplantation in rats.
BACKGROUND
Despite continued progress in the development of immunosuppressive agents, allograft rejection remains an important cause of morbidity and mortality after liver transplantation. We examined the effect of the deletion variant of hepatocyte growth factor (dHGF) on allograft rejection after liver transplantation.


METHODS
Male Dark Agouti rats (RT1a) were selected as donors and male Lewis rats (RT1l) as recipients for a rejection model. The recipients were divided into 2 groups after orthotopic liver transplantation (OLTx): in the dHGF group dHGF was given intravenously twice a day (1 mg/kg/day) after OLTx, whereas in the control group vehicle buffer was given intravenously daily twice after OLTx. The survival period, serum chemistry studies, and histopathologic findings were then compared between the 2 groups.


RESULTS
The mean survival period after OLTx in the dHGF group was significantly longer than that in the control group (21.4 +/- 1.3 days vs 11.8 +/- 0.4 days, P < .001). On the 10th posttransplant day the serum albumin level significantly improved in the dHGF group (P < .01), and the serum total bilirubin and aspartate aminotransferase levels were significantly lower in the dHGF group (P < .01 and P < .05, respectively). On the 10th posttransplant day a histologic examination revealed no apparent difference in the severity of rejection between the 2 groups. The number of proliferating cell nuclear antigen-positive hepatocytes in the dHGF group significantly increased (P < .01), whereas the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling-positive hepatocytes were significantly reduced in the dHGF group (P < .01) in comparison with those in the control group.


CONCLUSIONS
dHGF has an antiapoptotic property as well as a proliferative and protective effect on hepatocytes under allograft rejection. dHGF might serve as a novel agent for reducing the harmful effects of hepatic allograft rejection in rats.
Ikegami
T
T
Department of Surgery II, Kyushu University, Fukuoka, Japan.
Nishizaki
T
T
Uchiyama
H
H
Kakizoe
S
S
Yanaga
K
K
Sugimachi
K
K
D000595:Amino Acid Sequence; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D001663:Bilirubin / Q000097:blood; D006084:Graft Rejection / Q000473:pathology; D006085:Graft Survival; D017228:Hepatocyte Growth Factor / Q000235:genetics* / Q000502:physiology*; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008099:Liver / Q000737:chemistry / Q000473:pathology; D008111:Liver Function Tests; D016031:Liver Transplantation; D008297:Male; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D051381:Rats; D011917:Rats, Inbred Lew; D011919:Rats, Inbred Strains; D017384:Sequence Deletion; D012709:Serum Albumin / Q000032:analysis; D014184:Transplantation, Homologous
D018809:Proliferating Cell Nuclear Antigen; D012709:Serum Albumin; D017228:Hepatocyte Growth Factor; D001219:Aspartate Aminotransferases; D001663:Bilirubin