PMID- 17235585
OWN - NLM
STAT- MEDLINE
DCOM- 20071206
LR  - 20200914
IS  - 1435-2443 (Print)
IS  - 1435-2443 (Linking)
VI  - 392
IP  - 3
DP  - 2007 May
TI  - Alleviation of ischemia-reperfusion injury in rat liver transplantation by 
      induction of small interference RNA targeting Fas.
PG  - 345-51
AB  - BACKGROUND: Cellular apoptosis plays an important role in ischemia-reperfusion 
      (I/R) injury during organ transplantation. Synthetic small interference RNA 
      (siRNA) targeting apoptotic receptor Fas has proven effective to protect mice 
      against hepatitis and renal I/R injury. The objective of this study is to 
      investigate the silencing impact of Fas siRNA to alleviate I/R injury in rat 
      liver transplantation. MATERIALS AND METHODS: Rat hepatocytes (BRL cells) were 
      transfected with three pairs of synthesized Fas siRNA; cells untreated and 
      treated with GFP siRNA were taken as blank and siRNA control. The most effective 
      Fas siRNA was chosen for in vivo experiments. Syngeneic orthotopic liver 
      transplantation was performed in Fas siRNA group, siRNA control group, and blank 
      control group of Sprague-Dawley rats. There were 25 pairs of rats in each group. 
      siRNA transfection of donor rats was done with hydrodynamic injection method 48 h 
      before liver procurement. Blood and liver samples were collected for evaluation 
      of serum ALT levels, Fas protein and mRNA expression, and apoptosis by terminal 
      deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining, 1, 
      3, 6, 12, and 24 h after liver transplantation. RESULTS: Fas siRNA2, which 
      inhibited Fas gene expression much more than other siRNAs, was chosen for in vivo 
      experiment. The serum ALT levels of Fas siRNA group were much less than those of 
      blank and siRNA control groups 1, 3, 6, 12, and 24 h after blood reperfusion, 
      indicating diminishing ischemia-reperfusion injury. Donor livers in Fas siRNA 
      group had substantially less cell apoptosis. The expression of Fas mRNA and 
      protein was reduced dramatically in the Fas siRNA group compared with the other 
      two groups. CONCLUSION: Fas-mediated apoptosis play an important role in I/R 
      injury of rat liver transplantation. Silencing Fas by hydrodynamic injection of 
      siRNA holds therapeutic promise to limit I/R injury.
FAU - Li, X
AU  - Li X
AD  - Department of Liver Transplantation, The Third Affiliated Hospital of Sun Yat-sen 
      University, 600 Tianhe Road, Guangzhou, Guangdong Province 510630, China.
FAU - Zhang, J F
AU  - Zhang JF
FAU - Lu, M Q
AU  - Lu MQ
FAU - Yang, Y
AU  - Yang Y
FAU - Xu, C
AU  - Xu C
FAU - Li, H
AU  - Li H
FAU - Wang, G S
AU  - Wang GS
FAU - Cai, C J
AU  - Cai CJ
FAU - Chen, G H
AU  - Chen GH
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20070119
PL  - Germany
TA  - Langenbecks Arch Surg
JT  - Langenbeck's archives of surgery
JID - 9808285
RN  - 0 (Fas protein, rat)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (fas Receptor)
RN  - EC 2.6.1.2 (Alanine Transaminase)
SB  - IM
MH  - Alanine Transaminase/blood
MH  - Animals
MH  - Apoptosis/*genetics
MH  - Gene Expression
MH  - Gene Silencing
MH  - In Situ Nick-End Labeling
MH  - *Liver Transplantation
MH  - Male
MH  - RNA Interference
MH  - RNA, Small Interfering/genetics/*therapeutic use
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Reperfusion Injury/genetics/*prevention & control
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - fas Receptor/*antagonists & inhibitors/genetics/metabolism
EDAT- 2007/01/20 09:00
MHDA- 2007/12/07 09:00
CRDT- 2007/01/20 09:00
PHST- 2006/09/07 00:00 [received]
PHST- 2006/12/12 00:00 [accepted]
PHST- 2007/01/20 09:00 [pubmed]
PHST- 2007/12/07 09:00 [medline]
PHST- 2007/01/20 09:00 [entrez]
AID - 10.1007/s00423-006-0142-5 [doi]
PST - ppublish
SO  - Langenbecks Arch Surg. 2007 May;392(3):345-51. doi: 10.1007/s00423-006-0142-5. 
      Epub 2007 Jan 19.