AMINO ACID TRANSPORT AFTER SMALL BOWEL RESECTION

小肠切除术后的氨基酸转运

• 批准号: 6635016
• 负责人: HARRY CHARLES SAX
• 金额: $ 50.42万
• 依托单位: UNIVERSITY OF ROCHESTER
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-09-30 至 2005-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6635016
• 关键词: aminoacid transport; biological signal transduction; dietary aminoacid; epidermal growth factor; gastrointestinal absorption /transport; gastrointestinal function; gastrointestinal nutrient absorption; glutamine; growth factor receptors; hormone regulation /control mechanism; human tissue; immunoprecipitation; in situ hybridization; intestinal villi; intestine surgery; jejunectomy /duodenectomy /ileectomy; laboratory rabbit; membrane transport proteins; nutrition related tag; postoperative state; receptor binding; small intestines; somatotropin; tissue /cell culture; western blottings

Short bowel syndrome is a devastating clinical condition which leads to dehydration, muscle wasting, debilitation and death. Although the residual bowel has the capacity to adapt to its reduced surface area, this process is often inadequate and may require lifetime total parenteral nutrition, a modality with serious metabolic and economic consequences. Growth factors can improve adaptation in part by increasing the enterocyte's ability to transport luminal nutrients. A major nutrient glutamine (GLN) is the primary oxidative fuel for the enterocyte. The parenteral administration of epidermal growth factor (EGF) and/or human growth hormone (GH) increases sodium-dependent glutamine transport after 70% enterectomy in rabbits. The specific timing, route of administration, mechanisms of action, and potential synergistic effects of these two compounds remain to be elucidated. EGF binding activates the EGF receptor (EGFR). In cell suspensions derived from both human jejunum and C2BBE1cell line, EGF increases glutamine transport, upregulation is blocked by tyrosine kinase inhibitors which implicates a role for EGFR signaling transduction pathways. GH independently may also act through EGFR. It is hypothesized that the combination of EGF and GH upregulate sodium-dependent glutamine transport through EGFR signal transduction pathways. The specific aims of the proposal are to 1) optimize glutamine transport mediated by EGF/GH through EGFR in rabbits after massive enterectomy; 2) determine the involvement of EGFR signal transduction pathways in altering glutamine transport by EGF/GH exposure in C2BBE1cell line; 3) to investigate the effects of EGF/GH via EGFR in upregulating glutamine transport in human small bowel. The investigators plan to use three models of small bowel function: 70% enterectomy in the rabbit, the human cell line C2BBE1 in Transwells and human small bowel as an enterocyte suspension or as a neurovascularly intact loop. It is hypothesized that a better understanding of mechanisms involved in growth factor induced upregulation of nutrient transport will have significant clinical implications in developing safe and innovative strategies to treat patients with short bowel syndrome and other malabsorptive states.

短肠综合症是一种毁灭性的临床疾病