Prostaglandin E1 prevents liver failure after excessive hepatectomy in the rat by up-regulating Cyclin C, Cyclin D1, and Bclxl.
Prostaglandin E1 (PGE1) has wide-ranging effects on cytoprotection and may play a role in preventing liver failure following excessive hepatectomy. We examined the effect of PGE1 on hepatocyte apoptosis and liver regeneration after 95% hepatectomy in a rat model. PGE1 or vehicle was intravenously administered 30 minutes before and during hepatectomy. The extent of hepatocyte injury was evaluated by serum alanine aminotransferase and aspartate aminotransferase levels. To evaluate hepatocyte apoptosis and liver regeneration, terminal deoxynucleotidyl transferase dUTP nick end labeling staining and Ki67 labeling were performed. The expression levels of Bcl-xL, Bcl-2, Bax, Cyclin C, Cyclin D1, Cyclin E, p21, transforming growth factor-beta, plasminogen activator inhibitor-1, and glyceraldehyde-2-phosphate dehydrogenase mRNA were also examined by reverse transcription-polymerase chain reaction. Survival was improved in the PGE1 group (26.6%), whereas all rats in the vehicle group died within 60 hours. PGE1 significantly suppressed the release of alanine aminotransferase and aspartate aminotransferase at 12 hours postoperatively. Pretreatment with PGE1 significantly increased the Ki67-positive cell count and decreased the terminal deoxynucleotidyl transferase dUTP nick end labeling positive cell count after hepatectomy, and also significantly increased the expression levels of Bcl-xL, Cyclin C, and Cyclin D1. Our results suggest that pretreatment with PGE1 may increase survival following hepatectomy by salvaging the remaining liver tissue, which it does by inhibiting apoptosis and stimulating hepatocyte proliferation.
Ishibe
Atsushi
A
Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
Togo
Shinji
S
Kumamoto
Takafumi
T
Watanabe
Kazuteru
K
Takahashi
Takuji
T
Shimizu
Tetsuya
T
Makino
Hirochika
H
Matsuo
Kenichi
K
Kubota
Toru
T
Nagashima
Yoji
Y
Shimada
Hiroshi
H
D000410:Alanine Transaminase / Q000097:blood; D000527:Alprostadil / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001219:Aspartate Aminotransferases / Q000097:blood; D015153:Blotting, Western; D056745:Cyclin C; D019938:Cyclin D1 / Q000378:metabolism; D016213:Cyclins / Q000378:metabolism; D006498:Hepatectomy / Q000379:methods*; D022781:Hepatocytes / Q000187:drug effects; D020287:In Situ Nick-End Labeling; D017093:Liver Failure / Q000517:prevention & control*; D008115:Liver Regeneration / Q000187:drug effects; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D015854:Up-Regulation; D051020:bcl-X Protein / Q000378:metabolism
C494813:Bcl2l1 protein, rat; C503676:Ccnc protein, rat; C530106:Ccnd1 protein, rat; D056745:Cyclin C; D016213:Cyclins; D051020:bcl-X Protein; D019938:Cyclin D1; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D000527:Alprostadil