REDOX EFFECTS IN A MODEL OF AORTIC TISSUE INJURY

主动脉组织损伤模型中的氧化还原效应

• 批准号: 3087347
• 负责人: PETER R BERGETHON
• 金额: $ 7.48万
• 依托单位: BOSTON UNIVERSITY MEDICAL CAMPUS
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-08-01 至 1991-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3087347
• 关键词: aorta; biological models; elastases; extracellular matrix; glutathione; ischemia; myeloperoxidase; oxidation reduction reaction; radiotracer; tissue /cell culture; tocopherols; wound healing

The major goal is the development of a solid foundation in research techniques related to cell biology and biochemistry. Phase I of the training, which will focus on the development of a model for tissue injury and initial studies characterizing the effects of local reduction-oxidation potentials on both injury and response to injury, will be conducted in the laboratory of Dr. Carl Franzblau, Chairman of the Department of Biochemistry. Phase II, which will also be done under the tutelage of Dr. Franzblau, will focus on the clinically relevant questions of the role of reduction-oxidation environments in ischemia and hypoxia. By developing a cell culture model in which tissue extracellular matrix injury may be assessed, various local physical chemical influences may be studied. Cultured smooth muscle cells, with time, will form a multilayered cell system containing cells embedded in an extracellular matrix in a "hills and valleys" format. If this model is likened to the simplest of tissue specimens, it is hypothesized that injury of the extracellular matrix will provoke cellular responses leading to rapid, normal repair. In an effort to find a proposed method of general control, it is postulated that the local reduction-oxidation potential plays a role not only in the injury but also in the response to that injury. Within the confines of the culture system, a biochemically defined matrix will be produced which, in turn, can be injured in a controlled and measurable manner and ultimately repaired by the cells embedded in the matrix. Preliminary studies have been encouraging that such a system is feasible. The careful definition of this tissue culture system will then allow for the evaluation of the roles played independently or dependently by reduction-oxidation potentials and oxygen in the particular scenario of ischemia and hypoxia. The skills acquired in the first phase of the training program will allow Dr. Bergethon to further refine the techniques relating to measuring and manipulating redox potentials and then apply these techniques to both the smooth muscle culture as well as other cell types in an effort to study if local redox environments can significantly alter the damage done, both functional and mortal, and the subsequent response of cells to the injury.

主要目标是在研究方面奠定坚实的基础 与细胞生物学和生物化学相关的技术。第一期 培训，重点将是开发组织损伤模型 以及表征局部还原-氧化效应的初步研究 关于伤害和对伤害的反应的电位将在 科室主任卡尔·弗兰兹布劳博士的实验室 生物化学。第二阶段也将在Dr。 Franzblau，将重点关注与临床相关的问题，即 缺血和缺氧中的还原-氧化环境。 通过开发一种细胞培养模型，在该模型中组织细胞外基质 可以评估损伤，各种局部物理化学影响可以 学习。培养的平滑肌细胞，随着时间的推移，会形成多层 包含嵌入在细胞外基质中的细胞的细胞系统 “丘陵峡谷”的形式。如果把这个模型比作最简单的 组织标本，推测细胞外的损伤 基质将激发细胞反应，导致快速、正常的修复。在……里面 这是一种努力寻找一种拟议的总体控制方法，这是假设的 局部还原-氧化电位不仅在 不仅是对受伤的反应，也是对受伤的反应。在此范围内， 培养系统中，将产生一种生化定义的基质，在 反过来，可能会以可控和可测量的方式受到伤害，并最终 由嵌入在基质中的细胞修复。初步研究表明 这种制度是可行的，这一点一直令人振奋。 对这种组织培养系统的仔细定义将允许 对独立或依赖地扮演的角色的评价 还原-氧化电位和氧在特定情况下的 缺血和缺氧。在第一阶段中获得的技能 培训计划将允许Bergethon博士进一步完善技术 与测量和操作氧化还原电位有关，然后应用 这些技术既适用于平滑肌培养，也适用于其他细胞 类型，以努力研究本地氧化还原环境是否可以显著 改变造成的损害，包括功能性和致命性损害，以及随后的 细胞对损伤的反应。