The role of apoptosis during intestinal adaptation after small bowel resection

Background/Purpose: Adaptation after small bowel resection (SBR) is charact erised by a new set point in the balance of enterocyte proliferation and ap optosis. Apoptosis is gene directed. The authors hypothesised that the adap tive response is influenced positively by antiapoptotic gene products leg, bcl-2 gene-produced protein). The authors tested this hypothesis by studyin g the effect of bcl-2 overexpression on intestinal adaptation after SBR. Methods: Male bcl-2 transgenic mice, overexpressing bcl-2 in the small inte stinal epithelium, and wild type control mice underwent either a 75% mid-SB R, or a sham operation. The 4 experimental groups consisted of resection wi ld type (n = 8), transection wild type (n = 6), resection bcl-2 transgenic (n = 8), and transection bcl-2 transgenic (n = 8). Seven days postoperative ly small bowel was harvested; total weight, mucosal weight, and mucosal pro tein, DNA, and RNA content in jejunal and ileal tissue were determined to q uantitate the hyperplastic response. Results: Compared with sham-operated animals, SBR resulted in increased tot al jejunal weight; mucosal weight; and mucosal protein, DNA, and RNA conten t. Furthermore, in the SBR groups, the jejunal mucosal weight and mucosal p rotein and DNA content were significantly higher in the bcl-2 transgenic mi ce compared with the wild-type mice. No differences were observed between a ny 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 w eight 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 a nd mucosal protein, DNA, and RNA content compared with the wild-type mice. Conclusions: The results show that the murine SBR model is a true represent ation of the process of adaptation after SBR. Furthermore, major components of the adaptive response, both in the jejunum and in the ileum, are signif icantly more pronounced in the bcl-2 transgenic mice than in the wild-type control animals. Thus, it can be concluded that intestinal hyperplasia afte r 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. Copyright (C) 2000 by W.B. Saunders Company.