Improvement of recipient survival after small size graft liver transplantation in rats with preischemic manipulation or administering antisense against nuclear factor-kappaB.
The survival rate of small size graft liver transplantation (SSGLT) in rats is inversely related to graft volume. The present study aims to evaluate the protective effects of preischemic manipulation (PIM) and oligodeoxynucleotide (ODN) antisense against NF-kappaB on graft failure and animal survival. The protective effects of PIM and NF-kappaB ODN antisense were investigated in a rat SSGLT model. The graft function and survival of recipient animals over 3 weeks were monitored, and in situ staining for apoptotic cells in the graft tissue was examined. Both PIM and NF-kappaB antisense treatment significantly improved the survival of small graft-transplanted rats compared with the SSGLT group, lowered serum levels of alanine and aspartate aminotransferases, as well as tumor necrosis factor-alpha (TNF-alpha) levels, and minimized apoptotic cell counts in the liver sections. Moreover, the enhanced activation of NF-kappaB in the SSGLT group was diminished in both PIM and NF-kappaB antisense-treated groups. The findings suggest that enhanced NF-kappaB activation and TNF-alpha production may be involved in the ischemia/reperfusion-associated small size graft injury, and that PIM and antisense against NK-kappaB are effective in the attenuation of the small size graft injury, and improve the recipient animal survival.
Qian
Jiang-Ming
JM
Liver Transplant Section, Center for Organ Transplantation, Huashan Hospital, Fudan University, Shanghai, China.
Zhang
Hao
H
Wu
Xiao-Feng
XF
Li
Guo-Qiang
GQ
Chen
Xiao-Ping
XP
Wu
Jian
J
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D017209:Apoptosis; D001219:Aspartate Aminotransferases / Q000097:blood; D006085:Graft Survival; D008099:Liver / Q000473:pathology / Q000503:physiopathology; D016031:Liver Transplantation / Q000379:methods* / Q000401:mortality; D008297:Male; D016328:NF-kappa B / Q000235:genetics*; D016376:Oligonucleotides, Antisense / Q000627:therapeutic use*; D009929:Organ Size; D011184:Postoperative Period; D011300:Preoperative Care; D051381:Rats; D017207:Rats, Sprague-Dawley; D016019:Survival Analysis; D019737:Transplants; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D016328:NF-kappa B; D016376:Oligonucleotides, Antisense; D014409:Tumor Necrosis Factor-alpha; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase