GI MUCOSAL BARRIER IN HEALTH AND SURGICAL DISEASE

健康和外科疾病中的胃肠道粘膜屏障

• 批准号: 6725833
• 负责人: Susan J Hagen
• 金额: $ 9.64万
• 依托单位: BETH ISRAEL DEACONESS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-05-01 至 2003-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6725833
• 关键词: BCL2 gene /protein; CD95 molecule; Helicobacter; acid base balance; adenosine triphosphate; ammonia; apoptosis; biological signal transduction; cell biology; cell migration; cell morphology; cytotoxicity; electron microscopy; gastric mucosa; gastrointestinal infection; guinea pigs; host organism interaction; immunocytochemistry; intestinal mucosa; laboratory rabbit; mitochondria; necrosis; tissue /cell culture; wound healing

The major thrust of the proposed work is to identify at cellular level the mechanisms by which surface and other epithelial cells of the stomach and duodenum are injured and are repaired in circumstances commonly encountered in daily life. Simultaneously, factors which affect such injuries, both favorably and adversely, will be evaluated. The circumstances which allow or facilitate recovery of a cell, or those which lead to necrosis or programmed cell death are of special interest. Finally, the process of rapid repair of superficial injuries (restitution) and conditions which influence this restitution of epithelial continuity will be examined in detail. The investigations will be directed toward the following: a) To further understanding of the process of rapid epithelial repair (restitution) with particular reference to the role of intracellular pH, growth factors, and the extracellular matrix. Specifically, the following will be tested: whether activation of the Na+/H+ antiporter is essential for cell migration (restitution) to occur; whether the effect of growth factors to facilitate restitution is mediated by stimulation of the Na+/H+ antiporter; and whether various components of extracellular matrix influence restitution by affecting the Na+/H+ antiporter. b) To define both morphologically and biochemically in gastric mucosal epithelial cells differences between necrotic cell death and programmed cell death. c) To evaluate the reversibility of gastric mucosal epithelial injury of the type encountered in daily living or as a result of an infection such as that caused by Helicobacter pylori and to investigate mechanisms of protection against such injuries.

拟议工作的主要目标是在细胞水平上识别 胃表面和其他上皮细胞的机制 十二指肠损伤并在常见情况下修复 在日常生活中。同时，影响此类伤害的因素， 有利和不利都会进行评价。允许的情况 或促进细胞恢复，或导致坏死或 程序性细胞死亡受到特别关注。最后，过程 快速修复浅表损伤（恢复）和状况 将在以下方面检查对上皮连续性恢复的影响 细节。 调查将针对以下方面： a) 进一步 了解快速上皮修复（恢复）的过程 特别提及细胞内 pH 值、生长因子和 细胞外基质。具体来说，将测试以下内容： Na+/H+逆向转运蛋白的激活是否对细胞迁移至关重要 （恢复原状）发生；是否有促进生长因子的作用 恢复是通过刺激 Na+/H+ 反向转运蛋白介导的；和 细胞外基质的各种成分是否影响恢复 影响 Na+/H+ 逆向转运蛋白。 b) 从形态学和 胃粘膜上皮细胞生化差异 坏死性细胞死亡和程序性细胞死亡。 c) 评估 所遇到类型的胃粘膜上皮损伤的可逆性 在日常生活中或由于感染（例如由以下原因引起的感染） 幽门螺杆菌并研究其预防机制 这样的伤害。