FREE RADICALS, APOPTOSIS & TREATMENT OF DECUBITUS ULCERS

自由基、细胞凋亡

• 批准号: 2203933
• 负责人: RICHARD SALCIDO
• 金额: $ 15.07万
• 依托单位: UNIVERSITY OF KENTUCKY
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-01-01 至 1996-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2203933
• 关键词: aging; animal age group; animal old age; antioxidants; apoptosis; decubitus ulcer; disease /disorder model; electron spin resonance spectroscopy; enzyme activity; free radical oxygen; glutamate ammonia ligase; histopathology; hydroxyl radical; ischemia; juvenile animal; laboratory rat; mechanical pressure; reperfusion; salicylate; ultrasound blood flow measurement

This study is a joint effort of the departments of Rehabilitation Medicine, Pharmacology, and the Center for Biomedical Engineering. Despite the high prevalence and cost of pressure sores (PS), little scientific study has been directed towards the biochemical and molecular mechanisms of ulcer development, thus hampering effective treatment. Clinical studies on PS are difficult to assess because they are often qualitative, empirical, and uncontrolled. Our computer-controlled animal model allows for rigorous scientific analysis and evaluation of proposed PS treatments and preventatives. This system allows us to investigate the relationship between ischemia/reperfusion (IR) injury and free radical (FR) production by relating the biochemical events to the noninvasive measurement of blood flow utilizing a laser Doppler flow meter. Pressure ulcers are thought to develop as a result of IR/insult of the underlying subcutaneous tissue (muscle and/or adipose tissue). The current proposal is designed to directly determine the relationship between pressure/ischemia duration and frequency and the ultimate development of PS. Measurement of free radical (FR) production will verify the involvement of FR in the pathophysiology of PS development. FR spin- trapping compounds and other agents will be evaluated as to their ability to limit or prevent the development of PS. Our investigation of molecular causes of PS will continue with the testing of our hypothesis that apoptosis (programmed cell death) may play a significant role in the formation of decubitus ulcers. FR, apoptosis, and PS are intimately associated with cell death. If apoptosis is identified, several treatments would be implicated (i.e. use of inhibitors of protein and/or RNA synthesis).

这项研究是康复部门的共同努力， 医学、药理学和生物医学工程中心。 尽管压疮（PS）的患病率和成本很高， 科学研究一直致力于生物化学和分子生物学 溃疡发展的机制，从而阻碍有效治疗。 关于PS的临床研究很难评估，因为它们通常 定性的，经验的，不受控制的。 我们的电脑控制动物 该模型允许进行严格的科学分析和评估 PS治疗与预防 这个系统使我们能够调查 缺血再灌注损伤与自由基的关系 (FR)通过将生物化学事件与非侵入性 使用激光多普勒流量计测量血流。 压力 溃疡被认为是由于基础组织的IR/损伤而发展的， 皮下组织（肌肉和/或脂肪组织）。 现时的建议 旨在直接确定 压力/缺血持续时间和频率以及 PS. 自由基（FR）产生的测量将验证 FR参与PS发育的病理生理学。 FR自旋- 捕获化合物和其他试剂将被评估其能力， 以限制或防止PS的发展。 我们对分子生物学的研究 PS的原因将继续测试我们的假设， 细胞凋亡（程序性细胞死亡）可能在细胞凋亡中起重要作用。 褥疮的形成。 FR、凋亡和PS密切相关， 与细胞死亡有关。如果发现细胞凋亡， 将涉及（即使用蛋白质和/或RNA的抑制剂 合成）。