M Nagao1, S Isaji, M Iwata, Y Kawarada. 1. First Department of Surgery, Mie University School of Medicine, 2-174 Edobashi, Tsu, Mie, Japan.
Abstract
BACKGROUND/AIMS: 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. METHODOLOGY: 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.
BACKGROUND/AIMS: 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. METHODOLOGY: 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.