The remnant liver dysfunction after 84% hepatectomy in dogs.
OBJECTIVE
We have been investigating the mechanism of remnant liver dysfunction after extensive hepatectomy in a canine model since 1990. This study focused on the role of heat shock protein and hepatocyte apoptosis.


METHODS
Adult mongrel dogs were randomly divided into 3 groups: Group 1, sham operation; Group 2, 70% hepatectomy; and Group 3, 84% hepatectomy. Heat shock protein and hepatocyte apoptosis after hepatectomy were examined by using isolated hepatocytes and Kupffer cells.


RESULTS
Heat shock protein significantly increased in Groups 2 and 3, but rose much higher in Group 3. Examination of pure hepatocyte culture showed no apoptosis in Group 2, but significant apoptosis occurred in Group 3. In co-cultures of hepatocytes and Kupffer cells, induction of apoptosis in Group 2 was mild, but it increased earlier and reached very high levels in Group 3. The TNF-alpha level in co-culture supernatant was significantly higher in Group 3 than Group 2.


CONCLUSIONS
After extensive (84%) hepatectomy, apoptosis signal transduction predominates over anti-apoptosis signal transduction, despite high expression of heat shock protein in the remnant liver. Accordingly, the cytotoxic mechanism overcomes the cytoprotective mechanism, leading to significant induction of hepatocyte apoptosis and severe liver damage.
Nagao
M
M
First Department of Surgery, Mie University School of Medicine, 2-174 Edobashi, Tsu, Mie, Japan.
Isaji
S
S
Iwata
M
M
Kawarada
Y
Y
D000818:Animals; D017209:Apoptosis; D002470:Cell Survival; D002478:Cells, Cultured; D004285:Dogs; D005260:Female; D005434:Flow Cytometry; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D006498:Hepatectomy; D022781:Hepatocytes / Q000378:metabolism / Q000473:pathology*; D007728:Kupffer Cells / Q000378:metabolism / Q000473:pathology; D008099:Liver / Q000378:metabolism / Q000473:pathology* / Q000601:surgery*; D008297:Male; D008856:Microscopy, Fluorescence; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D018840:HSP70 Heat-Shock Proteins; D014409:Tumor Necrosis Factor-alpha