The intestinal mucosa is in a steady state of turnover as the rate of
cellular proliferation is balanced by the rate of cell death. While it is
accepted that adaptation after small bowel resection (SBR) results in increased
cellular proliferation, its effect on programmed cell death (apoptosis) is not
known. The purpose of this study was to determine the effect of adaptation
following SBR on rates of enterocyte apoptosis.
Methods: Male ICR mice underwent either 50% proximal SBR or sham operation
(bowel transection with reanastomosis only) and then sacrificed at 12 and 24 hr,
3 and 7 days. A proliferative index (PI) was derived in paraffin embedded ileum
by the percentage of crypt cells incorporating BrdU. A crypt apoptosis index
(AI) was quantitated by immunohistochemical labeling of DNA strand breaks,
confirmed morphometrically by propidium-iodide staining, and expressed as the
number of apoptotic bodies per crypt. Blinded scoring of 50 crypts per mouse was
performed in triplicate. Student's t-test was used to determine significance
between SBR and Sham groups at each time point.
Results: Adaptation after SBR resulted in significant increases in crypt
cell proliferation. Rates of enterocyte apoptosis were significantly increased
as well. Values are expressed as mean ± SEM.
Group (n) 12 hr 24 hr 3 days 7 days
PI (%)
Sham .24 ± .01 .24 ± .01 .24 ± .01 .26 ± .01
SBR (5) .4 ± .01* .34 ± .03# .39 ± .01* .43 ± .01*
AI (# Apoptotic
Bodies per Crypt)
Sham (5) .23 ± .03 .18 ± .03 .26 ± .03 .24 ± .02
SBR (5) .52 ± 03* .95 ± .08* 1.5 ± .14* 1.6 ± .09*
* P < 0.001; # P < 0.05
Conclusion: Adaptation following SBR increases both the rate of enterocyte
proliferation as well as the rate of apoptosis. Therapy directed toward reducing
apoptosis may provide a unique and more effective approach as a means to enhance
intestinal adaptation.
