The role of apoptosis during intestinal adaptation after small bowel resection

BACKGROUND/PURPOSE: Adaptation after small bowel resection (SBR) is characterised by a new set point in the balance of enterocyte proliferation and apoptosis. Apoptosis is gene directed. The authors hypothesised that the adaptive response is influenced positively by antiapoptotic gene products (eg, bcl-2 gene-produced protein). The authors tested this hypothesis by studying the effect of bcl-2 overexpression on intestinal adaptation after SBR. METHODS: Male bcl-2 transgenic mice, overexpressing bcl-2 in the small intestinal epithelium, and wild type control mice underwent either a 75% mid-SBR, or a sham operation. The 4 experimental groups consisted of resection wild type (n = 8), transection wild type (n = 6), resection bcl-2 transgenic (n = 8), and transection bcl-2 transgenic (n = 8). Seven days postoperatively small bowel was harvested; total weight, mucosal weight, and mucosal protein, DNA, and RNA content in jejunal and ileal tissue were determined to quantitate the hyperplastic response. RESULTS: Compared with sham-operated animals, SBR resulted in increased total jejunal weight; mucosal weight; and mucosal protein, DNA, and RNA content. Furthermore, in the SBR groups, the jejunal mucosal weight and mucosal protein and DNA content were significantly higher in the bcl-2 transgenic mice compared with the wild-type mice. No differences were observed between any of these parameters in the transection wild-type and transgenic mice. In the ileum, similar changes were observed. The differences between resected and transected wild-type mice were less pronounced, and only total ileal weight and mucosal protein content reached statistical significance. In the transgenic animals, all ileal variables, with the exception of mucosal RNA content, were significantly higher in the SBR group than in the transected group. SBR in the transgenic mice resulted in higher ileal mucosal weight and mucosal protein, DNA, and RNA content compared with the wild-type mice. CONCLUSIONS: The results show that the murine SBR model is a true representation of the process of adaptation after SBR. Furthermore, major components of the adaptive response, both in the jejunum and in the ileum, are significantly more pronounced in the bcl-2 transgenic mice than in the wild-type control animals. Thus, it can be concluded that intestinal hyperplasia after SBR is significantly enhanced by overexpression of the anti-apoptotic bcl-2 gene product. This finding should prompt further research on the effects of antiapoptotic interventions on adaptation after SBR.