Zhang W, Frankel W L, Adamson W T, Roth J A, Mantell M P, Bain A, Ziegler T R, Smith R J, Rombeau J L
Department of Surgery, Hospital of the University of Pennsylvania, Philadelphia 19104.
Transplantation. 1995 Mar 15;59(5):755-61. doi: 10.1097/00007890-199503150-00020.
The transplanted small intestine develops significant mucosal atrophy, impaired nutrient and water absorption, and increased bacterial translocation to mesenteric lymph nodes in rats maintained on elemental diets or total parenteral nutrition. This study determined the effects of administration of an peptide growth factor (insulin-like growth factor-I[IGF-I]) on the mucosal structure and barrier function of rat small bowel isografts. Thirty-six adult Lewis rats underwent either resection of the distal 60% of the small bowel and proximal colon followed by a 40-cm orthotopic jejunal isograft or proximal small bowel transection and distal small bowel resection to leave an analogous length of small intestine in control animals. All rats received an isocaloric, isonitrogenous, polymeric diet (200 kcal/kg/day, 2 gN/kg/day) by gastrostomy and were infused with either IGF-I (2.4 mg/kg/day) or vehicle by osmotic pumps subcutaneously. After 10 days of treatment, jejunal crypt cell production, mucosal morphometric indices, glucose and water absorption, body weight, and bacterial translocation to mesenteric lymph nodes (MLN) were measured. Jejunal mRNA content for IGF-I, IGF-I receptor, and IGF-binding proteins 3 and 4 (IGFBP-3,4) were determined by Northern blotting. Crypt cell production, villus height, crypt depth, and villus surface area were significantly increased in control and transplanted jejunum of rats infused with IGF-I when compared to animals given vehicle alone. Additionally, jejunal glucose absorption and water absorption were significantly improved in both IGF-I groups when compared with their respective vehicle controls. IGF-I infusion increased body weight in transplanted and control animals and markedly reduced bacterial translocation to MLN after small bowel transplantation. Jejunal levels of IGF-I mRNA were significantly increased in transplanted animals when compared to transected controls. IGF-I treatment significantly increased IGFBP-3 tissue mRNA levels in both transected and transplanted animals. These results demonstrate that IGF-I administration, after small bowel transplantation, improves mucosal structure and absorptive function and reduces bacterial translocation to MLN. IGF-I may have important effects in transplanted small bowel both as an endogenous and administered growth factor.
在采用要素饮食或全胃肠外营养的大鼠中，移植的小肠会出现明显的黏膜萎缩、营养物质和水分吸收受损，以及细菌易位至肠系膜淋巴结的情况。本研究确定了给予一种肽生长因子（胰岛素样生长因子-I [IGF-I]）对大鼠小肠同种异体移植黏膜结构和屏障功能的影响。36只成年Lewis大鼠，一部分接受远端60%小肠和近端结肠切除，随后进行40厘米原位空肠同种异体移植；另一部分接受近端小肠横断和远端小肠切除，以在对照动物中保留类似长度的小肠。所有大鼠均通过胃造口术接受等热量、等氮的聚合饮食（200千卡/千克/天，2克氮/千克/天），并通过皮下渗透泵输注IGF-I（2.4毫克/千克/天）或赋形剂。治疗10天后，测量空肠隐窝细胞生成、黏膜形态学指标、葡萄糖和水分吸收、体重以及细菌易位至肠系膜淋巴结（MLN）的情况。通过Northern印迹法测定空肠中IGF-I、IGF-I受体以及IGF结合蛋白3和4（IGFBP-3、4）的mRNA含量。与单独给予赋形剂的动物相比，输注IGF-I的大鼠对照组和移植空肠的隐窝细胞生成、绒毛高度、隐窝深度和绒毛表面积均显著增加。此外，与各自的赋形剂对照组相比，两个IGF-I组的空肠葡萄糖吸收和水分吸收均显著改善。输注IGF-I使移植和对照动物的体重增加，并显著减少小肠移植后细菌易位至MLN的情况。与横断对照组相比，移植动物空肠中IGF-I mRNA水平显著升高。IGF-I治疗显著增加了横断和移植动物中IGFBP-3组织mRNA水平。这些结果表明，小肠移植后给予IGF-I可改善黏膜结构和吸收功能，并减少细菌易位至MLN。IGF-I作为内源性和给予的生长因子，可能对移植的小肠具有重要作用。
