BACKGROUND. Starvation induces small bowel mucosal atrophy through increases in epithelial cell death and decreases in proliferation. We wondered whether these effects were greatest in the proximal or distal small bowel.
METHODS. 12 male 25-30 gm C57-BL6 mice were fasted with access to water; 10 mice were fed ad lib as controls. At 72 h, mice were sacrificed. Weight, protein content, and DNA content were determined on the proximal and distal portions of the small bowel. Histologic sections were assessed for villus height and crypt depth. Immunohistochemical analysis to quantitate proliferation and apoptosis was performed using labels for proliferating cell nuclear antigen (PCNA) and terminal deoxyuridine nick-ends (TUNEL).
RESULTS. Fasted mice lost 13.4% body weight compared to controls (p<.05). The % change in full-thickness weight was greater in the proximal (22%) than the distal gut (9%) (p<.05). Proliferation decreased in both proximal (11% decrease from control) and distal small bowel (15% decrease from control) (p<.05), with no significant differences between them. Apoptosis increased after fasting in both the proximal and distal small bowel (p<.05), however, the increase was greater in the proximal (60%) than the distal (38%) (p<.05). The location of cell death along the crypt-villus axis with fasting shifted toward the tip in the proximal bowel (p<.05), with no change in location in the distal segment.
CONCLUSION. The proximal small bowel was more responsive to starvation induced atrophy than the distal, which was due to greater increases in apoptotic cell death in cells located towards the tip of the villus.
Proximal Small Bowel Distal Small Bowel
Control Fasted Control Fasted
Full-Thickness Weight (mg/cm) 34.6±.7 26.9±.7* 22.1±.5 20.0±.8*
Protein Content (mg/cm) 2.9±.2 2.2±.1* 1.7±.04 1.5±.1
DNA content (mg/cm) 125.3±14.8 82.6±10.7* 149.2±45.1 106.9±15.5
Crypt Death (mm) 96.4±3.9 93.0±1.95 107.7±6.8 96.0±5.1
Villus Height (mm) 455.9±13.8 387.9±9.8* 197.7±14.8 171.9±4.9
* indicates significant change from control (p<.05).