PATHOPHYSIOLOGY OF RENAL ISCHEMIA, ANOXIA, HYPOPERFUSION

三种氧致肾损伤的病理生理学研究 将检查剥夺性缺血、缺氧和灌注不足， 对比。 我们还将研究干预措施的效果， 改变或防止缺氧的生化后果。 这些干预措施将阐明导致细胞 损伤 他们还将提供所需的宝贵信息， 开发旨在预防或改善急性肾功能衰竭的治疗方法 失败 这些研究将使用两种体外模型： 管悬浮液和离体肾脏制备物， 红细胞富集培养基 这些体外模型的使用将允许 肾缺血缺氧损伤机制研究进展 独立于诸如血压、交感神经系统 神经活动和全身激素 计划对灌注的分离小管和分离红细胞进行研究 肾（IEPK）将相互补充。 离体小管研究将 关注各种形式的缺氧对细胞的影响， 运输过程以及导致 细胞损伤 另一方面，IEPK将允许比较 缺血、缺氧、低灌注对完整器官的影响 功能和肾单位损伤的节段性模式。 这些研究 将决定是否干预，成功地改变了 运输异常和缺血或缺氧的生化后果 在管状制剂中，在完整的肾脏中产生类似的作用 并转化为肾小球滤过率、肾小管 钠处理和浓缩能力。 具体而言，该计划是：（1）检查缺血的影响， 缺氧在这两个模型和低灌注的IEPK。 （二） 确定细胞能量储存的消耗对 缺血缺氧损伤。 (3)研究形成的作用 氧自由基与缺血性损伤 (4)调查的重要性 通过检测缺血中细胞损伤后磷脂酶活化 刺激和抑制细胞增殖的药物的作用 磷脂酶活性对缺血性损伤的影响。 (5)阐明...的作用 缺血后介导损伤的细胞钙的改变。

The pathophysiology of renal injury induced by three forms of oxygen deprivation ischemia, anoxia and hypoperfusion will be examined and contrasted. We will also study the effect of interventions designed to modify or prevent the biochemical consequences of oxygen deprivation. These interventions will elucidate the mechanisms that lead to cellular injury. They will also provide valuable information needed for the development of therapies aimed at preventing or ameliorating acute renal failure. Two in vitro models for these studies will be used: an isolated proximal tubular suspension and an isolated kidney preparation perfused by an erythrocyte enriched medium. The use of these in vitro models will allow the study of intrarenal mechanisms of ischemic and anoxic injury independent of extraneous influences such as blood pressure, sympathetic nerve activity and systemic hormones. Studies planned for the isolated tubules and isolated erythrocyte perfused kidney (IEPK) will complement each other. The isolated tubule studies will focus on the effect of various forms of oxygen deprivation on cellular transport processes as well as on the biochemical events that lead to cellular injury. On the other hand, the IEPK will allow the comparison of the effects of ischemia, anoxia and hypoperfusion on integrated organ function and on the segmental pattern of nephronal injury. These studies will determine whether the interventions that successfully modify the transport abnormalities and biochemical consequence of ischemia or anoxia in the tubular preparation, produce similar effects in the intact kidney and are translated into improvement in glomerular filtration rate, tubular sodium handling, and concentrating ability. Specifically the plan is to: (1) Examine the effects of ischemia and anoxia in both these models and of hypoperfusion in the IEPK. (2) Determine the role played by depletion of cellular energy stores on ischemic and anoxic damage. (3) Study the role played by the formation of oxygen free radicals in ischemic injury. (4) Investigate the importance of phospholipase activation following cellular injury in ischemia by examining the effects of agents that both stimulate and inhibit cellular phospholipase activity on ischemic injury. (5) Elucidate the role of alterations in cellular calcium in mediating injury following ischemia.