[Effect of heme oxugenase-1 on delayed xenograft rejection: experiment of guinea pig-to-rat liver xenotransplantation].
OBJECTIVE
To investigate the effects and mechanism of heme oxygenase-1 (HO-1) in liver xenotransplantation and mechanism thereof.


METHODS
Thirty male guinea-pigs used as donors were injected intravenously with cobra venom factor (CVF) and then randomly divided into 3 groups 24 hours after: Group A injected intraperineally with NaCl, Group B injected intraperineally with cobalt-protoporphyrin (CoPP), heme oxygenase-1 inducer, and Group C injected intraperineally with CoPP and zinc protoporphyrin (ZnPP), HO-1 inhibitor zinc before their livers were harvested. Thirty male SD rats used as recipients underwent the above-mentioned treatment 24 hours before receiving the xenografts. Five pairs of guinea pigs and rats in each group underwent collection of blood and liver tissues 3 hours after the recovery of blood perfusion in the transplanted livers for detection of serum enzymes by biochemical methods and expression of HO-1 mRNA and protein in the transplanted livers by RT-PCR and Western blotting respectively. The other 5 pairs in each group were used to observe the survival time.


RESULTS
The survival time of Group B was 15.5 h +/- 3.8 h, significantly longer than those of Group A (7.3 h +/- 2.1 h) and Group C (6.7 h +/- 2.9 h, both P < 0.01). The values of ALT and LDH of Group B were significantly lower than those of Group A and C (all P < 0.05). HOI-1 mRNA expression was not detected or only expressed in trace amount in the livers of normal guinea pigs, expressed in a small amount in the transplanted livers of Group A. The expression of HO-1 mRNA and that of HO-1 protein in the transplanted livers of Group B were significantly higher than those of Group A (both P < 0.01), and the expression of HO-1 mRNA and that of HO-1 protein in the transplanted livers of Group C were not significantly different from those of Group A (both P > 0.05). Remarkable NF-kB band was detected in Groups A and C, and only weak NF-kB band was seen in Group B. The E-selectin expression was significantly lower in the transplanted livers of Group B than in those of Group A and C (both P < 0.05).


CONCLUSIONS
HO-1 delays the occurrence of delayed xenograft rejection in liver xenotransplantation. This effect depends, at least in part, on HO-1-mediated inhibition of endothelium activation in xenografts.
Song
Ning
N
Department of Surgery, Huashan Hospital & Institute of Organ Ttransplantation, Fudan University, Shanghai 200040, China.
Ni
Quan-xing
QX
Zhang
Qun-hua
QH
Shi
Chang-qing
CQ
Rui
Xiao-hui
XH
Shi
Liu-bin
LB
Shi
Wei
W
D000818:Animals; D004546:Elapid Venoms / Q000008:administration & dosage; D006084:Graft Rejection / Q000378:metabolism* / Q000517:prevention & control; D006168:Guinea Pigs; D051547:Heme Oxygenase-1 / Q000096:biosynthesis* / Q000235:genetics; D016031:Liver Transplantation / Q000276:immunology*; D008297:Male; D011524:Protoporphyrins / Q000008:administration & dosage; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D014183:Transplantation, Heterologous / Q000276:immunology*
D004546:Elapid Venoms; D011524:Protoporphyrins; D012333:RNA, Messenger; C016310:cobra venom factor; C017803:zinc protoporphyrin; C007095:cobaltiprotoporphyrin; D051547:Heme Oxygenase-1