Jonassen Julie A, Cao Lu-Cheng, Honeyman Thomas, Scheid Cheryl R
Department of Physiology, University of Massachusetts Medical School, Worcester 01655, USA.
Nephron Exp Nephrol. 2004;98(2):e61-4. doi: 10.1159/000080258.
This review summarizes our current understanding of intracellular events in the initiation of kidney stone formation, focusing on results from studies using renal epithelial cells in vitro. Such studies have shown that oxalate - either in crystalline or in soluble form - triggers a spectrum of responses in renal cells that favor stone formation, including alterations in membrane surface properties that promote crystal attachment and alterations in cell viability that provide debris for crystal nucleation. Activation of cytosolic PLA2 appears to play an important role in oxalate actions, triggering a signaling cascade that generates several lipid mediators (arachidonic acid, AA; lysophosphatidylcholine, Lyso-PC; ceramide) that act on key intracellular targets (mitochondria, nucleus). The net effect is increased production of reactive oxygen molecules (that in turn affect other cellular processes), an increase in cell death and an induction of a number of genes in surviving cells, some of which may promote proliferation for replacement of damaged cells, or may promote secretion of urinary macromolecules that serve to modulate crystal formation. A scheme is provided that explains how such oxalate-induced alterations could initiate stone formation in vivo.
本综述总结了我们目前对肾结石形成起始过程中细胞内事件的理解，重点关注体外使用肾上皮细胞的研究结果。此类研究表明，草酸盐——无论是晶体形式还是可溶形式——都会引发肾细胞中的一系列有利于结石形成的反应，包括促进晶体附着的膜表面特性改变以及为晶体成核提供碎片的细胞活力改变。胞质磷脂酶A2的激活似乎在草酸盐作用中起重要作用，引发一个信号级联反应，产生几种作用于关键细胞内靶点（线粒体、细胞核）的脂质介质（花生四烯酸，AA；溶血磷脂酰胆碱，Lyso-PC；神经酰胺）。最终结果是活性氧分子生成增加（进而影响其他细胞过程）、细胞死亡增加以及存活细胞中一些基因的诱导，其中一些基因可能促进受损细胞替代的增殖，或者可能促进调节晶体形成的尿大分子分泌。提供了一个示意图，解释了这种草酸盐诱导的改变如何在体内引发结石形成。
