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: 3087348
• 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/3087348
• 关键词: aorta; biological models; collagen; elastases; elastin; extracellular matrix; glutathione; ischemia; laboratory rabbit; laboratory rat; myeloperoxidase; oxidation reduction reaction; protein biosynthesis; 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.

主要目标是在研究中发展坚实的基础 与细胞生物学和生物化学有关的技术。 第一阶段 训练将集中于组织损伤模型的发展 以及表征局部还原氧化作用的初步研究 受伤和对伤害的反应的潜力将在 Carl Franzblau博士的实验室，部门主席 生物化学。 第二阶段，这也将在博士的指导下完成。 弗朗兹布劳（Franzblau）将重点关注有关临床相关的问题 缺血和缺氧的还原氧化环境。 通过开发细胞培养模型，其中组织外基质 可以评估伤害，各种局部物理化学影响可能是 研究。 随着时间的推移，培养的平滑肌细胞将形成多层 包含嵌入细胞外基质中的细胞的细胞系统 “山丘和山谷”格式。 如果该模型比喻为最简单的 组织标本，假设细胞外损伤 矩阵将引起细胞反应，从而导致快速，正常修复。 在 努力找到一种建议的通用控制方法，假设 局部还原氧化潜力不仅在 受伤，也对该受伤的反应。 在范围内 培养系统，将产生一个生化定义的矩阵，在 转弯，可以以受控和可测量的方式受伤，最终可以 由嵌入基质中的细胞修复。 初步研究 令人鼓舞的是，这样的系统是可行的。 然后，对该组织培养系统的仔细定义将允许 对角色的评估是独立或依赖的 在特定情况下的还原氧化潜力和氧气 缺血和缺氧。 在第一阶段获得的技能 培训计划将允许Bergethon博士进一步完善这些技术 与测量和操纵氧化还原电位有关，然后应用 这些技术既适用于平滑肌培养物以及其他细胞 努力研究当地氧化还原环境是否可以显着 更改功能性和致命的损害，以及随后的损害 细胞对损伤的反应。