Expression of Bcl-2 family reduces apoptotic hepatocytes after excessive hepatectomy

Excessive hepatectomy often causes fatal hepatic failure, but the mechanism is unknown. We used a novel protocol of partial 90 and 95% hepatectomy (PH x) to investigate this mechanism in 2 groups of rats. The 90% PHx rats surv ived, but the 95% PHx animals died of hepatic failure. In the latter, cytok ine (interleukin-6, tumor necrosis factor-a) levels and the apoptotic hepat ocyte count increased, and there were few mitotic cells. By contrast, in th e 90% PHx rats, the mitotic cell count increased, and more anti-apoptotic B cl-xL protein was expressed. These results demonstrate that expression of B cl-xL protein as an anti-apoptotic factor or regeneration factor contribute s to survival after 90% PHx. Using an adenovirus vector, the human bcl-2 ge ne (hbcl-2) was therefore transfected to DA rat livers where it was efficie ntly expressed, and then 95% PHx was performed. Liver damage was decreased and the apoptotic cell count decreased too, but the rats died. We concluded that transfection of the hbcl-2 gene partly prevents cytotoxicity (apoptos is), but cannot ensure survival. Thus, some other factor is required (e.g., a regeneration stimulator) to maintain life in these models. Copyright (C) 2001 S. Karger AG. Basel.