Sangild P T, Tappenden K A, Malo C, Petersen Y M, Elnif J, Bartholome A L, Buddington R K
Department of Human Nutrition, Royal Veterinary and Agricultural University, Copenhagen, Denmark.
J Pediatr Gastroenterol Nutr. 2006 Aug;43(2):160-7. doi: 10.1097/01.mpg.0000228122.82723.1b.
Parenteral nutrition is a critically important intervention for children with intestinal dysfunctions. However, total parenteral nutrition (TPN) with no enteral feeding is associated with small intestine atrophy and malabsorption, which complicate the transition to enteral nutrition. The objective of the present study was to evaluate the therapeutic potential of the intestinotrophic peptide glucagon-like peptide 2 (GLP-2), which reduces TPN-associated atrophy and maintains nutrient absorption in adult rats, for preventing nutrient malabsorption in neonates receiving TPN.
Term pigs obtained by cesarean delivery received from birth TPN alone (TPN; n = 7) or TPN with GLP-2 (25 nmol . kg(-1) . d(-1); GLP-2; n = 8) or were fed sow milk enterally (n = 7). The small intestine was removed on postnatal day 6 to measure morphological responses and absorption of glucose, leucine, lysine and proline by intact tissues and brush border membrane vesicles and to quantify the abundances of mRNA and protein for enterocyte glucose transporters (SGLT-1 and GLUT2).
Relative to TPN alone, administration of GLP-2 resulted in small intestines that were larger (P < 0.01), had greater abundances of mRNA and protein for SGLT-1, but not for GLUT2, and had higher capacities to absorb nutrients (P < 0.01). Moreover, the intestines of GLP-2 pigs were comparable in size and absorptive capacities with those of pigs fed sow milk enterally.
Providing GLP-2 to neonates receiving TPN prevents small intestine atrophy, results in small intestine absorptive capacities that are comparable to when nutrients are provided enterally and may accelerate the transition from TPN to enteral nutrition.
肠外营养是对肠道功能障碍儿童至关重要的干预措施。然而,完全肠外营养(TPN)且无肠内喂养与小肠萎缩和吸收不良相关,这会使向肠内营养的过渡变得复杂。本研究的目的是评估肠营养肽胰高血糖素样肽2(GLP - 2)的治疗潜力,该肽可减少成年大鼠TPN相关的萎缩并维持营养吸收,以预防接受TPN的新生儿出现营养吸收不良。
通过剖宫产获得的足月仔猪从出生起单独接受TPN(TPN组;n = 7)或接受TPN加GLP - 2(25 nmol·kg⁻¹·d⁻¹;GLP - 2组;n = 8),或经口喂养母猪奶(n = 7)。在出生后第6天取出小肠,测量其形态学反应以及完整组织和刷状缘膜囊泡对葡萄糖、亮氨酸、赖氨酸和脯氨酸的吸收,并量化肠上皮细胞葡萄糖转运蛋白(SGLT - 1和GLUT2)的mRNA和蛋白质丰度。
与单独接受TPN相比,给予GLP - 2导致小肠更大(P < 0.01),SGLT - 1的mRNA和蛋白质丰度更高,但GLUT2没有,并且吸收营养的能力更高(P < 0.01)。此外,GLP - 2组仔猪的小肠大小和吸收能力与经口喂养母猪奶的仔猪相当。
给接受TPN的新生儿提供GLP - 2可预防小肠萎缩,使小肠吸收能力与经肠内提供营养时相当,并可能加速从TPN向肠内营养的过渡。