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.

短肠综合征是毁灭性的临床状况 导致脱水，肌肉浪费，衰弱和死亡。虽然 残留的肠有能力适应其减少的表面积，此 过程通常不足，可能需要终身肠胃外 营养，一种具有严重代谢和经济后果的方式。生长 因素可以通过提高肠球细胞的能力来部分改善适应 运输腔内营养。主要的营养谷氨酰胺（GLN）是主要的 肠肠细胞的氧化燃料。表皮肠胃外管理 生长因子（EGF）和/或人类生长激素（GH）增加钠依赖性 兔70％肠切除术后的谷氨酰胺转运。特定的时机， 给药途径，作用机理和潜在协同作用 这两种化合物的作用仍有待阐明。 EGF结合激活 EGF受体（EGFR）。在源自两个人类空肠的细胞悬浮液中 和C2BBE1CELL线，EGF增加了谷氨酰胺的运输，上调被阻塞 通过酪氨酸激酶抑制剂，这暗示了EGFR信号的作用 转导途径。 GH独立也可以通过EGFR作用。这是 假设EGF和GH的组合上调钠依赖性 谷氨酰胺通过EGFR信号转导途径的转运。具体 该提案的目的是1）优化由EGF/GH介导的谷氨酰胺转运 大规模肠切除术后兔子的EGFR； 2）确定参与 EGFR信号转导途径在改变EGF/GH的谷氨酰胺转运方面 在C2BBE1CELL线中的暴露； 3）研究EGF/GH通过EGFR的影响 在人类小肠中上调谷氨酰胺运输中。调查人员 计划使用三种小肠功能：70％的肠切除术 兔子，人类细胞系C2BBE1在Transwells和人类小肠中作为一个 肠球悬浮液或神经血管完整的环。它是假设的 对生长因子诱导的机制有更好的理解 营养运输的上调将具有重大的临床意义 在制定安全和创新的策略以治疗肠子短的患者 综合征和其他疾病状态。