MECHANISMS OF CELL INJURY IN EXTRACORPOREAL SHOCK WAVE LITHOTRIPSY

体外冲击波碎石术中细胞损伤的机制

• 批准号: 6437390
• 负责人: James Alexander McAteer
• 金额: $ 29.59万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-03-01 至 2002-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6437390
• 关键词: biomechanics; cellular pathology; disease /disorder proneness /risk; epithelium; human tissue; iatrogenic disease; kidney disorder; kidney function; laboratory rabbit; lithotripsy; mechanical stress; morphology; oxidative stress; renal ischemia /hypoxia; renal tubule; tissue /cell culture; vascular endothelium

Renal injury is a well-documented consequence of shock wave lithotripsy (SWL) that for some patients (particularly the young and the elderly( may poe a significant health risk. How SWL causes tissue damage is not known. We do not known what physical mechanisms of shock wave (SW) impact are involved, and we do not know the cellular mechanisms of response to SW trauma. Our main objective is to determine how SWL causes tissue damage, and how the trauma of cellular injury leads to permanent changes in the kidney. Project 1 continues to make excellent progress in understanding the effects of SWL in vivo, but the complexity of the kidney makes the definition of specific cause-and-effect relationships difficult. Similarly, Projects 3 & 4 address the physical mechanisms of SW action, but SW interactions with the kidney are very complex. Project 2 provides a bridge to simplify these problems by using defined, in vitro biological systems. This will be a highly interactive collaborative investigation involving all projects of the SWL-PPG. Our approach is to use cultured cells, tissue slices and isolated in vitro systems to model shock wave response to the kidney tubular epithelium and vascular endothelium. We will: . assess for SWL activation of gene expression for transcription factors (cmyc, cfos, erg-1), heat shock proteins (hsp-70) and fibrogenic cytokines (TGF-b1, IL-1, TNF) involved in SW trauma and the SW-induced inflammatory response that leads to scar formation. . determine how conditions of SW treatment influence injury and affect cell response to subsequent trauma. . determine the role of cavitation and shear in cell damage.

肾损伤是冲击波碎石术的一个有据可查的后果 （SWL）对于一些患者（特别是年轻人和老年人（可能 POE 存在重大健康风险。 SWL 如何造成组织损伤尚不清楚。 我们不知道冲击波 (SW) 冲击的物理机制是什么 涉及，但我们不知道对 SW 反应的细胞机制 创伤。我们的主要目标是确定 SWL 如何导致组织损伤， 以及细胞损伤的创伤如何导致永久性改变 肾。 项目 1 在理解 SWL 在体内的影响，但肾脏的复杂性使得 定义具体的因果关系很困难。 同样，项目 3 和 4 解决了 SW 作用的物理机制， 但 SW 与肾脏的相互作用非常复杂。项目2提供 通过使用定义的体外生物学来简化这些问题的桥梁 系统。这将是一次高度互动的协作调查 涉及SWL-PPG的所有项目。我们的方法是使用有文化的 细胞、组织切片和分离的体外系统来模拟冲击波 对肾小管上皮和血管内皮的反应。我们 将要： 。评估转录因子基因表达的 SWL 激活 （cmyc、cfos、erg-1）、热休克蛋白 (hsp-70) 和纤维形成细胞因子 (TGF-b1、IL-1、TNF) 参与 SW 创伤和 SW 诱导的炎症 导致疤痕形成的反应。 。确定 SW 治疗条件如何影响损伤并影响 细胞对随后的创伤的反应。 。确定空化和剪切在细胞损伤中的作用。