Weinberg J M, Venkatachalam M A
Department of Internal Medicine, University of Michigan, Ann Arbor.
Miner Electrolyte Metab. 1992;18(2-5):123-32.
During the past several years studies using freshly isolated proximal tubules in suspension have contributed to understanding several of the major cellular processes underlying ischemic and related forms of acute renal failure. Tubules have a large capacity to augment their intracellular ATP content when supplemented with exogenous purines. This process has been shown to be mostly explained by adenosine uptake. Reductions of cell pH such as occur prominently during ischemia strongly protect tubules against a variety of insults. Increases of cytosolic free calcium to micromolar levels are highly damaging to tubules and do occur prior to lethal cell injury induced by ATP-depleting metabolic inhibitors, but do not critically determine the outcome in the latter setting. Given their ubiquitous occurrence and well-documented importance in a variety of systems, reactive oxygen metabolites play a surprisingly small role in oxygen deprivation-induced injury to isolated tubules. Several small neutral amino acids, glycine being the prototype and most potent, have a critical, constitutive effect to maintain tubule cell structural integrity during a variety of acute insults.
在过去几年中，使用新鲜分离的悬浮近端小管进行的研究有助于理解缺血性及相关形式急性肾衰竭背后的几个主要细胞过程。当补充外源性嘌呤时，小管具有大幅增加其细胞内ATP含量的能力。这一过程已被证明主要是由腺苷摄取来解释的。细胞pH值的降低，如在缺血期间显著发生的那样，能强烈保护小管免受各种损伤。胞质游离钙增加至微摩尔水平对小管具有高度损伤性，并且确实在由消耗ATP的代谢抑制剂诱导的致死性细胞损伤之前就会发生，但在后者情况下并非关键决定结果。鉴于活性氧代谢产物在各种系统中普遍存在且其重要性已得到充分证明，它们在缺氧诱导的离体小管损伤中所起的作用却出人意料地小。几种小的中性氨基酸，以甘氨酸为原型且最为有效，在各种急性损伤期间对维持小管细胞结构完整性具有关键的、组成性的作用。
