Alleviating ischemia-reperfusion injury in aged rat liver by induction of heme oxygenase-1.
BACKGROUND
Heme oxygenase-1 (HO-1), a cytoprotective protein, may be important in ameliorating hepatic ischemia-reperfusion (I/R) injury, a critical factor in the dysfunction of the aged liver after transplantation.


METHODS
We used hemin to overexpress HO-1 and analyze its effects in a model of I/R in aged livers used for orthotopic transplantation.


RESULTS
The SGOT levels in the hemin group were significantly lower than those of the saline treatment group. Hemin liver grafts showed markedly fewer apoptotic (TUNEL+) liver cells after reperfusion compared with the controls. The plasma nitric oxide levels in the hemin group were significantly lower than those in the control group. Unlike untreated or hemin + Znpp-treated orthotopic liver transplant controls, iNOS expression in the hemin group was almost absent at 12 and 24 hours, after reperfusion. In contrast, eNOS was comparable in hemin and saline orthotopic liver transplants. The increased levels of Bcl-2 expression compared with saline controls were most pronounced at 12 hours after transplantation. In contrast, caspase 3 was lower at 24 hours among the hemin-pretreated group compared with saline-treated liver transplant controls.


CONCLUSIONS
HO-1 alleviated the I/R injury in the aged liver by suppressing local expression of inducible nitric oxide synthase and by modulating pro- and antiapoptotic pathways.
Wang
X H
XH
Department of Hepatic Surgery, Liver Transplantation Center of Jiangsu Province, Nanjing, Jiangsu, China. skylancet@hotmail.com
Wang
K
K
Zhang
F
F
Li
X C
XC
Qian
X-F
XF
Cheng
F
F
Li
G Q
GQ
Fan
Y
Y
D000375:Aging; D000818:Animals; D017209:Apoptosis; D001219:Aspartate Aminotransferases / Q000097:blood; D004195:Disease Models, Animal; D006085:Graft Survival; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics*; D051547:Heme Oxygenase-1; D008102:Liver Circulation; D016031:Liver Transplantation / Q000473:pathology / Q000502:physiology*; D008297:Male; D019001:Nitric Oxide Synthase / Q000235:genetics; D052247:Nitric Oxide Synthase Type II; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000517:prevention & control*; D014185:Transplantation, Isogeneic
D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; D001219:Aspartate Aminotransferases