MECHANISMS OF MYOCARDIAL REPERFUSION INJURY--DIABETES

描述（改编自申请人的描述）：本研究的重点是 对再灌注炎症过程中中性粒细胞介导的组织损伤的影响 心肌根据之前的审查将申请修订为R29。 一般的前提是，再灌注损伤的严重程度似乎是一个 糖尿病患者的心脏比非糖尿病患者更危险。因此 中心假设是，增强的中性粒细胞募集和激活是 导致糖尿病心肌更易缺血/ 再灌注引起组织坏死。申请人建议调查 参与炎症反应的分子机制， 在db/db品系糖尿病小鼠和 链脲佐菌素处理的小鼠。实验计划将利用体内 冠脉结扎再灌注模型。单克隆抗体将 用于内皮细胞粘附分子的体内定量 （ECAM）。中性粒细胞聚集的程度、收缩功能和细胞 还将检查坏死，以评估糖尿病患者的脆弱性。 心脏缺血/再灌注损伤。申请人还打算评估 抗炎治疗对ECAM表达、白细胞募集和细胞增殖的影响 损害几个品系的转基因小鼠，作为细胞因子或 细胞粘附分子缺陷，也要测试的程度， 链脲佐菌素治疗后再灌注损伤。

DESCRIPTION (adapted from the applicant's description): This study is focused on the neutrophil mediated tissue injury during inflammation of the reperfused myocardium. The application is revised according to previous review as a R29. The general premise is that the severity of reperfusion injury appears to be a greater risk factor in hearts of diabetics than in non-diabetics. Thus, the central hypothesis is that enhanced neutrophil recruitment and activation is responsible for greater vulnerability of diabetic myocardium to ischemic/ reperfusion induced tissue necrosis. The applicant proposes to investigate the molecular mechanisms involved in the inflammatory response that is associated with reperfusion injury in a db/db strain of diabetic mice and in streptozotocin treated mice. The experimental plan will utilize an in vivo model of coronary artery ligation and reperfusion. Monoclonal antibodies will be used for in vivo quantification of endothelial cell adhesion molecules (ECAM). The extent of neutrophil accumulation, contractile function, and cell necrosis will also be examined to assess the vulnerability of the diabetic heart to ischemia/reperfusion damage. The applicant also intends to evaluate anti-inflammatory therapies on ECAM expression, leukocyte recruitment, and cell damage. Several strains of transgenic mice, as knockout models of cytokine or cell adhesion molecule deficiencies, are also to be tested for the extent of reperfusion injury following streptozotocin treatment.