MECHANISMS OF CELL INJURY IN EXTRACORPOREAL SHOCK WAVE LITHOTRIPSY

肾损伤是一个充分记录的后果冲击波碎石术 (SWL)对于一些患者（特别是年轻人和老年人）， 这是一个重大的健康风险。SWL如何引起组织损伤尚不清楚。 我们不知道冲击波（SW）冲击的物理机制是什么 参与，我们不知道细胞机制的反应，SW 外伤我们的主要目标是确定SWL如何引起组织损伤， 以及细胞损伤的创伤是如何导致 肾 项目1继续在了解 SWL在体内的作用，但肾脏的复杂性使得 具体的因果关系难以界定。 类似地，项目3和4解决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 一座桥梁，以简化这些问题，通过使用定义，在体外生物 系统.这将是一次高度互动的合作调查 涉及SWL-PPG的所有项目。我们的方法是使用培养的 模拟冲击波的细胞、组织切片和离体系统 对肾小管上皮和血管内皮的反应。我们 威尔： .评估SWL激活转录因子的基因表达 (cmyc... class ='class 1'>、CFOS、ERG-1）、热休克蛋白（HSP-70）和致纤维化细胞因子 TGF-β 1、IL-1、TNF参与SW创伤和SW诱导的炎症反应 导致疤痕形成的反应。 .确定SW治疗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。

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.