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B on liver cold ischemia-reperfusion injury
Thomas E. Starzl Transplantation Institute, Departments of 1 Surgery and 2 Pathology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania 15213
The
role of NF-
B, the rapid-response transcription factor for multiple
genes, in cold ischemia-reperfusion (I/R) injury was examined
after syngeneic transplantation of liver grafts. Lewis rat recipients
were killed 1-48 h after reperfusion of three different liver
grafts: 1) uninfected control, 2) infected ex
vivo with control adenoviral vector (AdEGFP), and 3)
infected ex vivo with AdI
B. In uninfected control livers, NF-
B
was activated biphasically at 1-3 and 12 h after reperfusion
with aspartate transaminase (AST) levels of 4,244 ± 691 IU/l. The
first peak of NF-
B activation associated with an increase of mRNA
for TNF-
, IL-1
, and IL-10. AdEGFP transfection resulted in
similar outcomes. Interestingly, AdI
B-transfected liver grafts
suffered more severe I/R injury (AST >9,000 IU/l). Transfected I
B
was detected in transplanted livers as early as 6 h, and this
correlated with the abrogation of the second, but not the first, peak
of NF-
B activation at 12-48 h and increased apoptosis.
Thus inhibition of the second wave of NF-
B activation in
I
B-transfected livers resulted in an increase of liver injury,
suggesting that NF-
B may have a dual role during liver I/R injury.
liver transplantation; preservation injuries; I
B; adenoviral
vector
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