Pre-Clinical Animal Models (PCAM) of Lung Inflammatory Injury

在袁博士和Moreno博士的领导下，设计了临床前动物模型核心(Core C) 为PPG研究人员提供严格定义和可重复性的急性肺损伤小鼠模型 ALI、机械通气性肺损伤(VILI)和放射性肺损伤(RILI)。核心将向前迈进 三个主要目标，第一个目标是提供全面的专业知识、培训、 设备和数据分析工具，以广泛研究和表征鞘脂在小鼠体内的作用 肺损伤模型。使用来自各种ALI、VILI和RILI模型的已发布协议和参数 (小鼠、大鼠、狗)，我们将使用最先进的技术来表征鞘磷脂在 炎症性肺损伤以及特定干预措施的效果，以提供对 新的治疗策略的有效性和机制，并促进基础研究向 临床领域。为此，岩芯将提供血管渗透率(KFC)的定量测量 白蛋白含量、炎症(组织髓过氧化物酶、炎性细胞)、水肿(伊文思蓝染料 外渗)和特定的生物标志物。第二个目标是为基因工程的人提供住房和照顾 将小鼠用于PPG并产生新的转基因小鼠。第三个目标将是 利用RNA沉默策略(SiRNA)，靶向肺内皮细胞(ACE结合)或脂质体 作为潜在的SIP受体的药物激动剂或拮抗剂/抑制剂的包封化和使用 急性肺损伤、机械通气或放射性肺损伤的治疗策略/方法 肺炎肺损伤模型。核心将完全访问并将利用 伊利诺伊大学芝加哥分校小动物成像核心(包括核磁共振和光学成像)。

The Pre-Clinical Animal Models Core (Core C), under the leadership of Drs. Yuan and Moreno, is designed to provide PPG investigators with rigorously defined and reproducible murine models of acute lung injury (ALI), ventilation-induced lung injury (VILI) and radiation-induced lung injury (RILI). The Core will advance three principal objectives with the first objective to provide a complete range of expertise, training, equipment, and data analysis tools to extensively study and characterize the role of sphingolipids in murine models of lung injury. Using published protocols and parameters from a variety of ALI, VILI and RILI models (mice, rats, dogs), we will employ state-of-the-art techniques to characterize the role of sphingolipids in inflammatory lung injury as well as the effects of specific interventions in order to provide insight into the efficacy and mechanisms of novel therapeutic strategies and to facilitate the translation of basic research to the clinical arena. To this end, the core will provide quantitative measurements of vascular permeability (Kfc) and albumin content, inflammation (tissue myeloperoxidase, inflammatory cells), edema (Evans blue dye extravasation) and specific biomarkers. The second objective is to house and care for the geneticallyengineered mice utilized in this PPG and to generate novel transgenic mice. The third objective will be to utilize RNA silencing strategies (siRNA), targeting the lung endothelium (ACE conjugated) or liposome encapsulated and the use of pharmacologic agonists or antagon-ists/inhibitors for SIP receptors as potential therapeutic strategies/approaches for acute lung injury, mechanical ventilation or radiation-induced pneumonitis lung injury models. The core will have full access to and will utilize resources available at the University of Illinois at Chicago Small Animal Imaging Core (including MRI and optical imaging).