Abstract
Objective To understand the role of heme oxygenase-1(HO-1)during ischemia reperfusion injury(IRI)after steatotie liver transplantation,we up-regulated the HO-1 expression of donors by gene transfection before transplantatiori and studied the effects and meehanisms of HO-1 during IRI. Methods Recombinant adenoviral vector encoding HO-1 gene(Ad5-HO-1)was constructed by using molecular biology method,and administered to donors yia penile vein at 48 h before transplantation.Livers of the donors were harvested and stored for 2 h at 4 ℃ in HTK solution before they were implanted into the recipients.Five groups were set up:control group(normal liver graft to be implanted),the mild steatosis liver control group(mild fatry liver graft to be implanted),the mild steatosis with Ad5-HO-1 pretreatment group(rats to be pretreated with Ad5-HO-1 and mild fatty Iiver graft to be implanted).the severe steatosis Iiver controI group(severe fatty liver graft to be implanted)and the severe steatosis with Ad5-HO-1 pretreatment group(rats to be pretreated with Ad5-HO-1 and severe fatty liver graft to be implanted).The survival rate of rats and Iiver graft pathological changes were observed.The levels of serum.ALT,AST,TB,activity of HO-1,and the expression levels of HO-1,Bcl-2,zinc finger protein A20,caspase-3 were assayed.Results Compared with the severe steatosis liver eontrol group,levels of serum ALT in the severe steatosis with Ad5-HO-1 pretreatment group were significantly reduced(P＜0.05);Activity of HO-1 in the severe steatosis with Ad5-HO-1 pretreatment group and the mild steatosis with Ad5-HO-1 pretreatment group were significantly increased(P＜0.05).Western blot and RT-PCR assays revealed that the expression of HO-1.Bcl-2 and A20 in the severe steatosis with Ad5-HO-1 pretreatment group was stronger than in the severe steatosis liver control group(P＜0.05),but that of Caspase-3 weaker.The survival rate in the severe steatosis with Ad5-HO-1 pretreatment group at 1 st,7th,and 21 st day was respectively 66.7%(4/6),50%(3/6),50%(3/6),and that in the severe steatosis liver control group was respectively 33.3%(2/6),16.7%(1/6),16.7%(1/6)(P＜0.05).Conclusion HO-1 gene transfer could attenuate rat steatotic livers from IRI after rat liver transplantation. Key words: Heme oxygenase; Liver transplantation; Reperfusion injury; Animals,genetically modified; Rats
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