Administration of NF-?B decoy oligodeoxynucleotides palliates ischemia-reperfusion injury of rat liver graft / 中华器官移植杂志

ABSTRACT

Objective To investigate the protective effect and mechanisms of NF-?B decoy oli- godeoxynucleotides(ODNs)on rat liver graft following ischemia-reperfusion injury.Methods Ani- mals were randomly divided into 3 groups(n=8 in each group)control group,ischemia-reperfusion (IR)group,and decoy ODNs group,in which donor grafts were transfected with 120?g NF-?B decoy ODNs before graft procurement.Following 2 h of reperfusion,Kupffer cells(KCs)were isolated,and NF-?B biding activity was detected with electrophoretic mobility shift assay(EMSA),and TNF-?、IL- 6 mRNA expression was assayed by using RT-PCR method.Meanwhile,the liver and serum samples were collected,the histopathologic change of liver was examined by light microscope,and liver func- tion was analyzed.Results The NF-?B biding activity,TNF-?,IL-6 mRNA expression,and the ALT,TBIL levels in serum were significantly increased following 2 h of reperfusion in IR group as compared with those in control group(P＜0.01).A large amount of degeneration and necrosis in hep- atocytes accompanied with obvious congestion in hepatic sinusoid occurred.However,these tested in- dexes were significantly ameliorated in decoy ODNs group as compared with those in IR group(P＜0.01),and the architecture of hepatic lobules was remained.Conclusions KCs NF-?B activation fol- lowing reperfusion plays an important role in IRI in liver transplantation.Decoy strategy shows appar- ent effect on suppression of NF-?B activation,and thus inhibits the production of downstream cyto- kines,which protects the liver graft from IRI.