Lieberthal W, Koh J S, Levine J S
Evans Medical Foundation of Medical Research, Department of Medicine, Boston Medical Center, MA 02118, USA.
Semin Nephrol. 1998 Sep;18(5):505-18.
Renal tubular cells that are lethally injured after an acute ischemic or nephrotoxic insult to the kidney can die by necrosis or apoptosis. Necrosis is usually the result of overwhelming and severe cellular ATP depletion. In contrast, there are many potential causes of apoptosis in acute renal failure (ARF). These include cytotoxic events not severe enough to induce necrosis, a relative deficiency of renal growth factors, and loss of cell-matrix or cell-cell adhesive interactions. In some situations, receptor-mediated events induced by tumor necrosis factor-alpha (TNF-alpha) or Fas (CD95) may play a role in apoptosis in ARF. Necrosis and apoptosis are distinct morphologically and biochemically. Necrosis results in an early loss of plasma membrane integrity, the release of injurious substances from the cytosol, and an inflammatory reaction in the surrounding tissue that is readily detected morphologically. In contrast, apoptosis is characterized by progressive cell shrinkage with condensation and fragmentation of nuclear chromatin. Apoptotic cells ultimately break up into plasma membrane-bound vesicles called "apoptotic bodies" that are rapidly phagocytosed by macrophages and neighboring epithelial cells. In experimental models of ARF in vivo, apoptosis of renal tubular cells has been shown to occur in two distinct phases. The first phase of apoptosis occurs early on, between 12 and 48 hours after the acute ischemic or nephrotoxic insult. The second phase of apoptosis occurs many days later, during the recovery phase of ARF. Tubular cell apoptosis occurring shortly after the acute insult probably contributes to tubular cell loss and the tubular dysfunction associated with ARF. In contrast, the apoptosis associated with the recovery phase has been postulated to contribute to the remodeling of injured tubules and to facilitate their return to a normal structural and functional state. Therapeutic interventions that inhibit or promote apoptosis of renal tubular cells have the potential for minimizing renal dysfunction and accelerating recovery after ARF.
在肾脏受到急性缺血或肾毒性损伤后，发生致命性损伤的肾小管细胞可通过坏死或凋亡的方式死亡。坏死通常是细胞内三磷酸腺苷（ATP）大量严重耗竭的结果。相比之下，急性肾衰竭（ARF）中凋亡的潜在原因有很多。这些原因包括细胞毒性事件严重程度不足以诱导坏死、肾生长因子相对缺乏以及细胞与基质或细胞与细胞之间黏附相互作用的丧失。在某些情况下，由肿瘤坏死因子-α（TNF-α）或Fas（CD95）诱导的受体介导事件可能在ARF的凋亡中起作用。坏死和凋亡在形态学和生物化学上是不同的。坏死导致质膜完整性早期丧失，细胞溶质中有害物质释放，以及周围组织发生炎症反应，这在形态学上很容易检测到。相比之下，凋亡的特征是细胞逐渐萎缩，核染色质浓缩和碎片化。凋亡细胞最终分解为被称为“凋亡小体”的质膜结合囊泡，这些囊泡会迅速被巨噬细胞和邻近的上皮细胞吞噬。在体内ARF的实验模型中，肾小管细胞凋亡已被证明发生在两个不同阶段。凋亡的第一阶段发生在早期，即在急性缺血或肾毒性损伤后12至48小时之间。凋亡的第二阶段发生在数天后，即ARF的恢复阶段。急性损伤后不久发生的肾小管细胞凋亡可能导致肾小管细胞丢失以及与ARF相关的肾小管功能障碍。相比之下，与恢复阶段相关的凋亡被认为有助于受损肾小管的重塑，并促进其恢复到正常的结构和功能状态。抑制或促进肾小管细胞凋亡的治疗干预措施有可能将肾功能障碍降至最低，并加速ARF后的恢复。
