Abstract
Massive small bowel resection (SBR) results in a significant increase in intestinal epithelial cell (EC) proliferation as well as apoptosis. Because the site of SBR (proximal (P) vs. distal (D)) affects the degree of intestinal adaptation, we hypothesized that different rates of EC apoptosis would also be found between P-SBR and D-SBR models. Wild-type C57BL/6J mice underwent: (1) 60% P-SBR, (2) 60% D-SBR, or (3) SHAM-operation (transaction-reanastomosis) at the mid-gut point. Mice were sacrificed after 7 days. EC apoptosis was measured by TUNEL staining. EC-related apoptotic gene expression including intrinsic and extrinsic pathways was measured with reverse transcriptase-polymerase chain reaction. Bcl-2 and bax protein expression were analyzed by Western immunoblotting. Both models of SBR led to significant increases in villus height and crypt depth; however, the morphologic adaptation was significantly higher after P-SBR compared to D-SBR (P<0.01). Both models of SBR led to significant increases in enterocyte apoptotic rates compared to respective sham levels; however, apoptotic rates were 2.5-fold higher in ileal compared to jejunal segments (P<0.01). P-SBR led to significant increases in bax (pro-apoptotic) and Fas expression, whereas D-SBR resulted in a significant increase in TNF-alpha expression (P<0.01). EC apoptosis seems to be an important component of intestinal adaptation. The significant difference in EC apoptotic rates between proximal and distal intestinal segments appeared to be due to utilization of different mechanisms of action.