Sukhotnik Igor, Slijper Nadav, Karry Rachel, Shaoul Ron, Coran Arnold G, Lurie Michael, Shiloni Eitan, Mogilner Jorge G
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.
Pediatr Surg Int. 2007 May;23(5):397-404. doi: 10.1007/s00383-006-1862-x.
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.
近期证据表明,蛙皮素(BBS)参与正常小肠生长和分化的调节。本研究的目的是评估BBS对大鼠大规模小肠切除术后肠上皮细胞更新的影响。雄性Sprague-Dawley大鼠分为三个实验组:假手术组大鼠进行肠横断和再吻合,短肠综合征(SBS)组大鼠进行75%小肠切除,SBS-BBS组大鼠进行肠切除,并从术后第3天至第14天接受皮下注射剂量为20μg/kg的BBS治疗,每日一次。在术后第15天测定空肠和回肠的肠道适应参数(肠和黏膜重量、黏膜DNA和蛋白质、绒毛高度和隐窝深度)、肠上皮细胞增殖和肠上皮细胞凋亡。采用RT-PCR技术测定回肠黏膜中Bax和Bcl-2基因表达。使用非参数Kruskal-Wallis方差分析进行统计分析,P值小于0.05被认为具有统计学意义。与SBS组动物相比,BBS治疗导致回肠肠和黏膜重量、回肠黏膜DNA和蛋白质、空肠和回肠绒毛高度、空肠隐窝深度以及空肠和回肠增殖指数显著增加。与假手术组动物相比,SBS组大鼠回肠中Bax和Bcl-2表达显著增加,同时细胞凋亡显著增加。与SBS组动物相比,SBS-BBS组大鼠回肠中Bax和Bcl-2表达显著降低,凋亡指数降低。总之,在SBS大鼠模型中,BBS增强肠上皮细胞更新并刺激肠道结构适应。Bax表达降低可能是BBS对肠上皮细胞凋亡抑制作用的原因。