VASOACTIVE LIPOXYGENASE PRODUCTS IN GLOMERULAR INJURY

肾小球疾病是人类肾衰竭的主要原因。 因此，肾小球损伤的介质一直是 广泛研究的目标。 审查联合国各机构的作用 血管活性肽，儿茶酚胺，补体级联， Hageman因子相关系统，氧代谢物， 环氧合酶产物和其他损伤介质导致 认识到肾小球滤过功能受损， 选择性渗透功能是高度复杂的 这些不同系统之间的相互作用。 尽管有许多 关于每个调解人的贡献的争议 参与，共识存在的核心作用， 多形性白细胞和巨噬细胞/单核细胞 起源于启动和维持肾小球功能障碍。 这 这一发现引起了人们对生物活性 在这些细胞活化过程中释放的化合物，包括 花生四烯酸的环氧合酶和脂氧合酶（LO）产物 酸 拟议研究的目的是试图定义 花生四烯酸的LO产物在介导 肾小球灌注、滤过和 在选定的临床相关的 实验性肾小球损伤模型。 实验 方法包括：（1）检查，通过肾小球 微穿刺和葡聚糖清除技术，肾小球 对外源性硫肽白三烯的反应 (LTC4 D4和E4）和15-LO产物脂氧素A和B。 （二） 确定这些化合物在介导肾小球疾病中的作用， 肾毒性血清和内毒素诱导的 肾小球损伤，通过测量其内源性 产生率和选择性拮抗其生理 行动 (3)评价肾小球细胞的能力 亚群，以产生这些化合物， 刺激. 肾小球内LO活性的存在， 分离的肾小球上LT受体的鉴定， 由我们和其他人演示LO产品的有效效果 对生理和生理条件下肾小球和系膜细胞功能 病理生理条件，使他们的调查 肾小球效应可能有益。

Glomerular disease is a major cause of renal failure in man. For this reason, the mediators of glomerular injury have been the target of extensive research. Examination of the roles of vasoactive peptides, catecholamines, the complement cascade, Hageman factor-related systems, oxygen metabolites, cyclooxygenase products, and other mediators of injury has led to the realization that impairment of glomerular filtration and permselectivity function is the end-result of highly complex interactions among these various systems. Despite much controversy regarding the contribution of each of the mediators involved, consensus exists as to the central role of the polymorphonuclear leukocyte and cells of macrophage/monocyte origin in initiating and perpetuating glomerular dysfunction. This finding has generated interest in the biologically active compounds released during the activation of these cells, including the cyclooxygenase and lipoxygenase (LO) products of arachidonic acid. The aim of the proposed studies is to attempt a definition of roles of LO products of arachidonic acid in mediating the impairment of glomerular perfusion, filtration, and permselectivity functions seen in selected, clinically relevant models of experimental glomerular injury. The experimental approach involves: (1) Examining, through glomerular micropuncture and dextran clearance techniques, the glomerular responses to exogenously administered sulfidopeptide leukotrienes (LTC4, D4, and E4) and the 15-LO products, lipoxins A and B. (2) Defining the roles of these compounds in mediating glomerular dysfunction in nephrotoxic serum and endotoxin-induced glomerular injury, through measurement of their endogenous generation rates and selective antagonism of their physiologic actions. (3) Assessing the capacity of glomerular cell subpopulations to generate these compounds upon appropriate stimulation. The presence of LO activity within the glomerulus, the identification of LT receptors on isolated glomeruli, and the demonstration by us and others of potent effects of LO products on glomerular and mesangial cell function under physiologic and pathophysiologic conditions, render the investigation of their glomerular effects potentially rewarding.