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AMINO ACID TRANSPORT AFTER SMALL BOWEL RESECTION

小肠切除术后的氨基酸转运

基本信息

批准号：
6717698
负责人：
HARRY CHARLES SAX
金额：
$ 51.93万
依托单位：
UNIVERSITY OF ROCHESTER
依托单位国家：
美国
项目类别：
财政年份：
1994
资助国家：
美国
起止时间：
1994-09-30 至 2006-04-30
项目状态：
已结题

项目摘要

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

项目成果

期刊论文数量（9）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Growth hormone and epidermal growth factor together enhance amino acid transport systems B(0,+) and A in remnant small intestine after massive enterectomy.

生长激素和表皮生长因子共同增强大肠切除术后残余小肠中的氨基酸转运系统 B(0, ) 和 A。

DOI：
10.1016/s0022-4804(03)00185-9
发表时间：
2003
期刊：
The Journal of surgical research
影响因子：
0
作者：
Ray,EdwardC;Avissar,NellyE;Vukcevic,Dubravka;Toia,Liana;Ryan,CharlotteK;Berlanga-Acosta,Jorge;Sax,HarryC
通讯作者：
Sax,HarryC

Methods used to study intestinal nutrient transport: past and present.

用于研究肠道营养物质运输的方法：过去和现在。

DOI：
10.1006/jsre.2002.6527
发表时间：
2002
期刊：
The Journal of surgical research
影响因子：
0
作者：
Ray,EdwardC;Avissar,NellyE;Sax,HarryC
通讯作者：
Sax,HarryC

Specific nutrients in intestinal failure: one size fits no one.

肠道衰竭中的特定营养素：一种方法不适合任何人。

DOI：
10.1053/j.gastro.2005.11.047
发表时间：
2006
期刊：
Gastroenterology
影响因子：
29.4
作者：
Sax,HarryC
通讯作者：
Sax,HarryC

Growth hormone and epidermal growth factor together enhance amino acid transport systems B0,+ and A in remnant small intestine after massive enterectomy.

生长激素和表皮生长因子共同增强大肠切除术后残余小肠中的氨基酸转运系统 B0 和 A。

DOI：
10.1016/s0022-4804(03)00225-7
发表时间：
2003
期刊：
The Journal of surgical research
影响因子：
0
作者：
Ray,EdwardC;Avissar,NellyE;Vukcevic,Dubravka;Toia,Liana;Ryan,CharlotteK;Berlanga-Acosta,Jorge;Sax,HarryC
通讯作者：
Sax,HarryC

Epidermal growth factor and/or growth hormone induce differential, side-specific signal transduction protein phosphorylation in enterocytes.

表皮生长因子和/或生长激素诱导肠细胞中差异性、侧特异性信号转导蛋白磷酸化。