Effect of massive small bowel resection on the bax/bcl- w ratio and enterocyte apoptosis

Following small bowel resection (SBR), the remnant intestine undergoes adaptation. Enterocyte proliferation is increased and counterbalanced by increased rates of apoptosis. To elucidate a mechanism for increased enterocyte apoptosis, this study tested the hypothesis that the ratio between pro-apoptotic Bax and pro-survival Bcl- w correlates with the apoptosis that occurs following SBR. Mice (C57B1/6; n = 76) underwent a 50% proximal SBR or sham operation. After 12 hours and 1,2,3, and 7 days, the ileum was removed, the apoptotic index (apoptotic bodies/crypt) was recorded, and the messenger RNA and protein for Bax and Bcl-w were quantified. The apoptotic index was equivalent in the sham and SBR mice at 12 hours; however, it was significantly elevated following SBR at every other day measured. The ratio of Bax to Bcl-w messenger RNA relative to sham operation increased after SBR at 24 hours, decreased by day 3, and returned to baseline levels by 1 week. The protein ratio showed an increase by day 1, which remained elevated through day 7. An augmented ratio of Bax to Bcl-w messenger RNA and protein corresponded with the increase in enterocyte apoptosis. Alterations in the expression ratio of these genes may play a role in establishing a new homeostatic set point between proliferation and apoptosis during adaptation. Supported by grants F32 DK09882 (Dr. Stern) and RO-1 DK53234 (Dr. Warner) from the National Institutes of Health and by a grant from the Children’s Hospital Campaign for Children Fund, Children’s Hospital Medical Center, Cincinnati, Ohio. Presented at the Fortieth Annual Meeting of The Society for Surgery of die Alimentary Tract, Orlando, Fla., May 16–19, 1999.