Bombesin stimulates enterocyte turnover following massive small bowel resection in a rat.
Recent evidence suggests that bombesin (BBS) is involved in modulation of growth and differentiation of normal small intestine. The purpose of the present study was to evaluate the effects of BBS on enterocyte turnover after massive small bowel resection in a rat. Male Sprague-Dawley rats were divided into three experimental groups: Sham rats underwent bowel transection and re-anastomosis, short bowel syndrome (SBS) rats underwent a 75% small bowel resection, and SBS-BBS rats underwent bowel resection and were treated with BBS given subcutaneously at a dose of 20 mug/kg, once daily, from postoperative day 3 through 14. Parameters of intestinal adaptation (bowel and mucosal weights, mucosal DNA and protein, villus height and crypt depth), enterocyte proliferation and enterocyte apoptosis were determined in jejunum and ileum on day 15 following operation. RT-PCR technique was used to determine Bax and Bcl-2 gene expression in ileal mucosa. Statistical analysis was performed using the non-parametric Kruskal-Wallis ANOVA test, with P less than 0.05 considered statistically significant. Treatment with BBS resulted in a significant increase in ileal bowel and mucosal weight, ileal mucosal DNA and protein, jejunal and ileal villus height, jejunal crypt depth, and jejunal and ileal proliferation index compared to SBS-animals. SBS rats showed a significant increase in Bax and Bcl-2 expression in ileum that was accompanied by a significant increase in cell apoptosis compared to sham animals. SBS-BBS rats demonstrated a significant decrease in Bax and Bcl-2 expression in ileum and a decrease in apoptotic index compared to SBS-animals. In conclusion, in a rat model of SBS, BBS enhances enterocyte turnover and stimulates structural intestinal adaptation. Decreased Bax expression may be responsible for the inhibitory effect of BBS on enterocyte apoptosis.
Sukhotnik
Igor
I
Department of Pediatric Surgery, Pediatrics and Pathology, Bnai Zion Medical Center, Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, 47 Golomb St., P.O.B. 4940, Haifa 31048, Israel. igor-dr@internet-zahav.net
Slijper
Nadav
N
Karry
Rachel
R
Shaoul
Ron
R
Coran
Arnold G
AG
Lurie
Michael
M
Shiloni
Eitan
E
Mogilner
Jorge G
JG
D000222:Adaptation, Physiological / Q000187:drug effects / Q000502:physiology; D000704:Analysis of Variance; D000818:Animals; D017209:Apoptosis; D001839:Bombesin / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D020895:Enterocytes / Q000187:drug effects* / Q000648:ultrastructure; D015870:Gene Expression / Q000187:drug effects; D007413:Intestinal Mucosa / Q000187:drug effects*; D007421:Intestine, Small / Q000187:drug effects / Q000601:surgery* / Q000648:ultrastructure; D008297:Male; D018377:Neurotransmitter Agents / Q000494:pharmacology*; D009929:Organ Size / Q000187:drug effects; D011184:Postoperative Period; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D012778:Short Bowel Syndrome / Q000601:surgery; D013997:Time Factors; D051028:bcl-2-Associated X Protein / Q000378:metabolism
C494828:Bax protein, rat; D018377:Neurotransmitter Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D001839:Bombesin