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POLYAMINES IN THE REGULATION OF GASTROINTESTINAL GROWTH

多胺调节胃肠生长

基本信息

批准号：
3446015
负责人：
EDWARD R SEIDEL
金额：
$ 3.94万
依托单位：
EAST CAROLINA UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
1984
资助国家：
美国
起止时间：
1984-08-01 至 1987-07-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/3446015
关键词：
Zollinger Ellison syndrome autonomic nervous system cell growth regulation enteric bacteria fatty acids gastritis gastrointestinal epithelium gastrointestinal hormones gastrointestinal neoplasms gastrointestinal system growth /development hormone regulation /control mechanism intestinal mucosa pernicious anemia polyamines postnatal growth disorder

项目摘要

The presence of food in the gut produces both direct and indirect effects on the growth of the gastrointestinal mucosa. Becasue ingestion of foodstuffs leads to increased desquamation of the epithelium and changes in luminal or local nutrition, direct effects on growth are produced when food moves through the gut after a meal. Indirect effects of a meal include release of GI hormones, increased secretions and increased activity of the autonomic nervous system. There may be a common mechanism which mediates both types of stimulation. The polyamines are a group of ubiquitously distributed polycations which are required for normal cell growth and proliferation. Preliminary studies have shown that they are involved in the regulation of mucosal growth. These data demonstrate that 1) there is a proximal to distal gut gradient of polyamine metabolism, 2) the aliphatic amine, ethylamine, has direct trophic effects in the gut, 3) the trophic response to intestinal obstruction has, as a required event, the induction of polyamine metabolism. These observation may explain 1) the proximal to distal gut gradient of villus height and crypt depth, 2) the role of amines, both aliphatic and polyamines, as regulators of GI mucosal growth, 3) the mechanism whereby the hormones of the gut exert their trophic in GI tissues, and 4) the as yet unexplained adaptive response of the gut to intestinal surgery. It is proposed to study and define the role of amines as regulators of mucosal growth. Initial experiments are designed to localize the areas of the gut in which amine metabolism is important to growth. It will also be necessary to study amine metabolism in the bacteria of the intestinal microflora as amines secreted from these cells may have direct effects on mucosal growth. It will be determined whether the hormones of the GI tract induce polyamine metabolism and whether this step is required for expression of their trophic effects. Finally, the role of amines as mediators of the adaptive response to intestinal surgery will be defined in various animal models of postsurgical hyperplasia and hypertrophy. The importance of a thorough understanding of GI growth is underscored by the realization that many diseases of the bowel, e.g., Zollinger-Ellison syndrome, chronic gastritis, pernicious anemia and the growth of cancers of the alimentary canal, are accompanied by disorders of gastrointestinal growth.

食物在肠道中的存在会产生直接和间接的影响对胃肠道粘膜的生长有影响。因为摄入了食物导致上皮脱落增加，管腔或局部营养，对生长的直接影响，当食物在饭后通过肠道。一顿饭的间接影响包括胃肠道激素的释放，分泌物的增加和活动的增加，自主神经系统。可能有一种共同的机制，这两种刺激。多胺是一组普遍存在的分布的聚阳离子是正常细胞生长所需的，增殖初步研究表明，粘膜生长的调节。这些数据表明：（1）多胺代谢的近端到远端肠道梯度，2）脂肪族胺，乙胺，在肠道中有直接的营养作用，3）营养对肠梗阻的反应，作为一个必要的事件，诱导多胺代谢。这些观察可以解释1）近端远端肠梯度绒毛高度和隐窝深度，2）的作用胺，脂肪族和多胺，作为GI粘膜生长的调节剂， 3)肠道激素在胃肠道中发挥营养作用的机制组织，和4）尚未解释的适应性反应的肠道，肠道手术建议研究和确定胺的作用作为粘膜生长的调节剂。最初的实验旨在定位肠道中胺代谢重要的区域增长也将有必要研究胺代谢在肠道菌群的细菌作为从这些细胞分泌的胺可能对粘膜生长有直接影响。将决定是否胃肠道的激素诱导多胺代谢，表达其营养作用需要一个步骤。最后胺类物质在肠道手术适应性反应中的作用将在各种术后增生的动物模型中定义，肥厚深入了解GI生长的重要性是认识到许多肠道疾病，例如， Zollinger-Ellison综合征，慢性胃炎，恶性贫血和消化道癌症的生长，伴随着胃肠道生长