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: 6570863
• 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: 2002
• 资助国家: 美国
• 起止时间: 2002-03-01 至 2003-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6570863
• 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公认的后果。 (SWL)对于一些患者(特别是年轻人和老年人(可能 POE是一个重大的健康风险。SWL如何导致组织损伤尚不清楚。 我们不知道冲击波撞击的物理机制是什么。 参与其中，我们不知道对Sw反应的细胞机制 精神创伤。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 肾脏。 项目1继续在理解 SWL在体内的作用，但肾脏的复杂性使 很难定义具体的因果关系。 同样，项目3和4涉及西南地区行动的物理机制， 但Sw与肾脏的相互作用是非常复杂的。项目2提供 通过使用已定义的体外生物学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 涉及苏丹人民解放军-人民保护小组的所有项目。我们的方法是用有教养的 模拟冲击波的细胞、组织切片和体外分离系统 对肾小管上皮和血管内皮细胞的反应。我们 将： 。转录因子基因表达的SWL激活评估 (cMYC、CFOS、ERG-1)、热休克蛋白(HSP-70)和纤维化细胞因子 (转化生长因子-β1、IL-1、肿瘤坏死因子)参与短波创伤及短波致炎作用 导致疤痕形成的反应。 。确定短波治疗的条件如何影响损伤和影响 细胞对后续创伤的反应。 。确定空化和剪切在细胞损伤中的作用。