Pathophysiology of renal tubular obstruction: therapeutic role of synthetic RGD peptides in acute renal failure.
Pathophysiology of renal tubular obstruction: therapeutic role of synthetic RGD peptides in acute renal failure.
复制标题
肾小管阻塞的病理生理学：合成 RGD 肽在急性肾衰竭中的治疗作用。
DOI：
10.1038/ki.1995.426
复制
发表时间：
1995
影响因子：
19.6
通讯作者：
Goligorsky,MS
中科院分区：
文献类型：
--
作者：
Noiri,E;Romanov,V;Forest,T;Gailit,J;DiBona,GF;Miller,F;Som,P;Oster,ZH;Goligorsky,MS
别迦摩的盖伦在他的著名著作《自然能力》中引入了“吸引力”[δλκηz]的概念，作为肾脏功能的主要模式：他声称，血液对肾脏的吸引力导致尿液的产生[1]。尽管吸引力的概念在盖伦的古代尚未得到证实，并且被后人完全拒绝作为肾功能的机械解释，但吸引力的概念不仅以修改的形式保留下来，而且已成为现代生理学的基石原理之一，以及我们目前对血小板聚集、转移、免疫识别和伤口愈合等多种过程的病理生理学的理解，仅举几例，所有这些都由粘附分子控制。在这里，我们回顾了粘附分子在肾小管梗阻病理生理学中的作用，重点关注整合素及其新近认识的功能。 Oliver、MacDowell 和 Tracy 进行的一系列精美的显微解剖研究将肾小管梗阻在急性肾衰竭 (ARF) 发病机制中的重要性带到了中心舞台 [2]。通过对不同 ARF 模型中近端肾小管压力进行零伺服压力监测，研究人员为静水管内压力升高以及停流和估计肾小球毛细血管压力不变提供了确凿证据，进一步证实了该综合征的肾小管阻塞成分[3-5]。因此，得出的结论是，肾小管阻塞和近端肾小管压力升高平衡了肾小球滤过压力，从而导致持续性少尿。据推测，坏死的上皮细胞为阻塞管腔的管型提供了基质。然而，最近在患有 ARF 的患者和实验动物的尿液中发现了存活的上皮细胞，这对假设的模式提出了质疑，并表明上皮细胞脱离的可能性是肾小管梗阻发展的一个重要因素 [6-8]。在接下来的讨论中，我们将提出这个主题，提供有关缺血性 ARF 肾小管梗阻的可能机制的数据，以及抑制肾小管梗阻的治疗策略和益处，并提出这个新兴研究领域的一些未来方向。
In his famous workOn the Natural Faculties, Galen of Pergamum introduced the idea of “attraction” [δλκηζ] as the principal mode of kidney function: the attraction of blood to the kidney, he claimed, results in the production of urine [1]. Though unproven in Galen's ancient times and entirely rejected by the later generations as a mechanistic explanation of renal function, the concept of attraction has not only survived, albeit in a modified form, but has become one of the cornerstone principles of modern physiology and our current understanding of the pathophysiology of processes as diverse as platelet aggregation, metastases, immune recognition and wound healing, to name a few, all of which are governed by adhesion molecules. Here we review the role of adhesion molecules in the pathophysiology of tubular obstruction, focusing on the integrins and their newly recognized function in it.The importance of renal tubular obstruction in the pathogenesis of acute renal failure (ARF) was brought to center stage by a series of elegant microdissection studies by Oliver, MacDowell and Tracy [2]. Using servo-null pressure monitoring of the proximal tubular pressure in diverse models of ARF, investigators have provided solid evidence for the elevation in hydrostatic intratubular pressure concomitant with the unchanged stop-flow and estimated glomerular capillary pressures, further confirming the tubulo-obstructive component of this syndrome [3–5]. It has been concluded, therefore, that tubular obstruction and elevated proximal tubular pressure equilibrate glomerular filtration pressure, thus leading to the persisting oliguria. Necrotic epithelial cells have been postulated to provide the matrix for casts obstructing the tubular lumen. Recent findings of viable epithelial cells in the urine of patients and experimental animals with ARF, however, cast doubt on the postulated schema and suggest the possibility of epithelial cell detachment as an important contributor to the development of tubular obstruction [6–8].In the following discussion we develop this theme, providing data on the possible mechanism(s) of tubular obstruction in ischemic ARF, and on the therapeutic strategies in and benefits of inhibiting tubular obstruction, and suggest some future directions of this fledgling field of investigations.