Sukhotnik Igor, Mogilner Jorge G, Lerner Aaron, Coran Arnold G, Lurie Michael, Miselevich Iness, Shiloni Eitan
Department of Pediatric Surgery, Rappaport Faculty of Medicine, Bnai Zion Medical Center, Technion-Israel Institute of Technology, 47 Golomb St, P.O. Box 4940, Haifa 31048, Israel.
Pediatr Surg Int. 2005 Jun;21(6):460-5. doi: 10.1007/s00383-005-1461-2. Epub 2005 May 26.
The nitric oxide precursor L-arginine (ARG) has been shown to influence intestinal structure and absorptive function. It is also well known that the route of administration modulates the effects of ARG. The present study evaluated the effects of parenteral ARG on structural intestinal adaptation, cell proliferation, and apoptosis in a rat model of short bowel syndrome (SBS). Male Sprague-Dawley rats were divided into three experimental groups: Sham rats underwent bowel transection and reanastomosis, SBS rats underwent a 75% small bowel resection, and SBS-ARG rats underwent a 75% small bowel resection and were treated with ARG given subcutaneously at a dose of 300 mug/kg, once daily, from days 3 to 14. Parameters of intestinal adaptation, enterocyte proliferation, and enterocyte apoptosis were determined on day 15 following operation. The SBS rats demonstrated a significant increase in jejunal and ileal bowel and mucosal weight, villus height and crypt depth, and cell proliferation index compared with the sham group. The SBS-ARG animals demonstrated lower ileal bowel and mucosal weights, jejunal mucosal DNA and ileal mucosal protein, and jejunal and ileal villus height and crypt depth compared with SBS animals. The SBS-ARG rats also had a lower cell proliferation index in both jejunum and ileum and a greater enterocyte apoptotic index in ileum compared with the SBS-untreated group. In conclusion, in a rat model of SBS, parenteral arginine inhibits structural intestinal adaptation. Decreased cell proliferation and increased apoptosis are the main mechanisms responsible for decreased cell mass.
一氧化氮前体L-精氨酸（ARG）已被证明会影响肠道结构和吸收功能。众所周知，给药途径会调节ARG的作用。本研究评估了肠外给予ARG对短肠综合征（SBS）大鼠模型肠道结构适应性、细胞增殖和细胞凋亡的影响。雄性Sprague-Dawley大鼠分为三个实验组：假手术组大鼠接受肠横断和重新吻合术，SBS组大鼠接受75%小肠切除术，SBS-ARG组大鼠接受75%小肠切除术，并在术后第3天至第14天每天皮下注射剂量为300μg/kg的ARG进行治疗。在术后第15天测定肠道适应性、肠上皮细胞增殖和肠上皮细胞凋亡的参数。与假手术组相比，SBS组大鼠空肠和回肠肠段及黏膜重量、绒毛高度和隐窝深度以及细胞增殖指数显著增加。与SBS组动物相比，SBS-ARG组动物的回肠肠段和黏膜重量、空肠黏膜DNA和回肠黏膜蛋白以及空肠和回肠绒毛高度和隐窝深度较低。与未治疗的SBS组相比，SBS-ARG组大鼠空肠和回肠的细胞增殖指数也较低，回肠的肠上皮细胞凋亡指数较高。总之，在SBS大鼠模型中，肠外给予精氨酸会抑制肠道结构适应性。细胞增殖减少和细胞凋亡增加是导致细胞量减少的主要机制。
