CORE--RENAL INJURY MODEL

核心--肾损伤模型

• 批准号: 6564383
• 负责人: Michael Kashgarian
• 金额: $ 14.1万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-12-01 至 2002-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6564383
• 关键词: biomedical facility; cellular pathology; disease /disorder model; histopathology; laboratory rat; model design /development; molecular pathology; renal ischemia /hypoxia

Description: (Adapted from the application) The overall objective of this Core is to develop and define in vivo experimental systems which can test how the protein-protein interactions which are the main focus of the individual projects at the cellular level are disrupted in the whole kidney of the intact animal during ischemic and hypoxic injury and the mechanisms by which normal renal structure (and function) is restored during recovery. While it is important to understand how individual cell membrane proteins interact with specific cytoskeletal elements on a molecular level and how these interactions are disrupted during ATP depletion, it is necessary to analyze these changes at different levels of organization including the cellular, organ and whole animal to fully understand their pathobiological importance. This principle has been clearly demonstrated in so called knockout experiments where more often than not the result at the whole animal level is less dramatic than anticipated, demonstrating a level of complexity and redundancy which cannot be appreciated fully in isolated cell culture systems. In an in vivo model both cellular and systemic processes are needed to achieve full functional physiologic recovery and to understand interrelationships between vascular and epithelial structures, growth factors and cytokines and hemodynamic and cellular alterations which can influence the nature of response to injury and recovery. Thus, animal models provide the only way that the integration, relative importance and hierarchy of the specific molecular and cellular responses that occur in ischemic renal injury and in the critical components of recovery can be determined. The provision of animal models by the core will provide a center for the application of basic cell and molecular biologic studies to the clinical problem of acute renal failure.

描述：（从应用程序改编）该核心的总体目标是在体内实验系统中开发和定义，该系统可以测试蛋白质 - 蛋白质相互作用如何在整个细胞级别中破坏单个项目的主要重点缺血性和低氧损伤期间完整动物的肾脏以及在恢复过程中恢复正常肾脏结构（和功能）的机制。虽然重要的是要了解单个细胞膜蛋白如何在分子水平上与特定的细胞骨架元素相互作用，以及在ATP耗竭期间如何破坏这些相互作用，但有必要在不同的组织中分析这些变化，包括细胞，器官和全动物。充分了解他们的病理学重要性。在所谓的敲除实验中已经清楚地证明了这一原理，在这种实验中，整个动物水平的结果通常比预期的要少，证明了一定的复杂性和冗余水平，而在孤立的细胞培养系统中无法完全理解。在体内模型中，需要细胞和全身过程，以实现全功能生理恢复，并了解血管和上皮结构，生长因子和细胞因子以及血液动力学和细胞改变之间的相互关系，从而影响对损伤和康复的反应的性质。因此，动物模型提供了唯一的方法，即可以确定缺血性肾脏损伤和恢复关键成分的特定分子和细胞反应的整合，相对重要性和层次结构。核心为动物模型提供的提供将为应用基本细胞和分子生物学研究应用于急性肾衰竭的临床问题的中心。