Core

核

• 批准号: 7160744
• 负责人: Lewis C Becker
• 金额: $ 16.28万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-04-01 至 2011-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7160744
• 关键词: animal colony; biomedical facility; heart; inflammation; injury; ischemia; laboratory mouse; laboratory rat; model; myocardial ischemia /hypoxia; proteins; reperfusion; role; transcription factor

The Animal Core will provide state-of-the-art models of myocardial ischemia-reperfusion injury in the intact mouse. Myocardial infarction will be created by coronary artery occlusion in the anesthetized open chest animal, followed by reperfusion for various periods of time in either acute or survival models. In some experiments, mice will undergo thoracotomy, implantation of a ligature around a coronary artery, and exteriorization of the ligature to allow for closed chest occlusion-reperfusion of the coronary artery 1-2 weeks later. Left ventricular function will be measured by serial echocardiography and detailed pressure-volume loop studies will be done at the time of sacrifice. Myocardial infarct size will be measured by tetrazolium staining, followed by digital photography, and quantitative image analysis. Myocardial tissue samples will be analyzed histologically in collaboration with the Pathology Core. These models will be used by Projects 1, 3, 4, and 5 to assess the importance of certain regulatory processes on the extent of myocardial injury in ischemia-reperfusion, and on the role of hypoxia inducible factor-1 (HIF1) mediated stem cell cardiac repair, by comparing results in wild type control mice with genetically modified or pharmacologically treated mice. The Animal Core will also provide a microvascular ischemia-reperfusion model in the cremaster muscle of the rat or mouse, using videomicroscopy to quantify leukocyte rolling, adherence, and transmigration in the microcirculation. These experiments will be performed in the laboratory of Dr Giuseppe Ambrosio in Perugia, Italy. The model will be applied to rats transfected with decoy oligonucleotides or interferring RNA to inhibit specific signaling pathways, and in mice with selected genetic mutations. The model will be used by Projects 1, 2, 3, and 5.

Animal Core 将提供最先进的完整心肌缺血再灌注损伤模型 老鼠。麻醉的开胸动物会因冠状动脉闭塞而产生心肌梗塞， 随后在急性或生存模型中进行不同时间段的再灌注。在一些实验中，小鼠 将进行开胸手术、在冠状动脉周围植入结扎线以及将结扎线取出 以允许 1-2 周后进行胸腔闭塞-冠状动脉再灌注。左心室功能 将通过系列超声心动图进行测量，届时将进行详细的压力-容量环研究 的牺牲。通过四唑染色测量心肌梗塞面积，然后进行数码摄影， 和定量图像分析。将与以下机构合作对心肌组织样本进行组织学分析 病理学核心。项目 1、3、4 和 5 将使用这些模型来评估某些项目的重要性 缺血再灌注中心肌损伤程度的调节过程以及缺氧的作用 通过比较野生型对照小鼠和小鼠的结果，诱导因子 1 (HIF1) 介导干细胞心脏修复 经过基因改造或药物治疗的小鼠。 Animal Core 还将提供大鼠提睾肌的微血管缺血再灌注模型 或小鼠，使用视频显微镜来量化白细胞在 微循环。这些实验将在佩鲁贾朱塞佩·安布罗西奥博士的实验室进行， 意大利。该模型将应用于转染诱饵寡核苷酸或干扰RNA的大鼠，以抑制 特定的信号通路，以及具有选定基因突变的小鼠。该模型将由项目 1 使用， 2、3 和 5。