Khan Saeed R
Department of Pathology, College of Medicine, University of Florida, Gainesville 32610-0275, USA.
Nephron Exp Nephrol. 2004;98(2):e55-60. doi: 10.1159/000080257.
Normal urinary environment is inhibitory to crystallization. Occasional crystals are internalized by the renal epithelial cells and sequestered to lysosomes or externalized into the interstitium to be handled by the inflammatory cells. Elevated levels of oxalate and calcium oxalate crystals, however, provoke renal cells to increase the synthesis of osteopontin, bikunin, heparan sulfate proteoglycan, monocyte chemoattractant protein-1, and prostaglandin E(2), which are known mediators of the inflammatory processes and extracellular matrix production. Osteopontin and bikunin are also modulators of crystallization. Exposed renal epithelial cells are often injured and go through apoptosis and/or necrosis initiating a cascade of events leading to further crystallization, crystal retention and development of stone nidi. Reactive oxygen species are produced during the interactions between the oxalate/crystals and renal cells and are responsible for the various cellular responses. Calcium oxalate crystal deposition in the rat kidneys also activates the renin-angiotensin system. Both oxalate and calcium oxalate crystals selectively activate p38 mitogen-activated protein kinase in the exposed tubular cells. Extracellular environment changes from one that inhibits crystal nucleation, growth, aggregation and retention to that, which promotes these processes.
正常的尿液环境可抑制结晶形成。偶尔形成的晶体可被肾上皮细胞内化，并被隔离到溶酶体中，或被排到间质中由炎症细胞处理。然而，草酸盐和草酸钙晶体水平升高会促使肾细胞增加骨桥蛋白、 bikunin、硫酸乙酰肝素蛋白聚糖、单核细胞趋化蛋白-1和前列腺素E(2)的合成，这些都是已知的炎症过程和细胞外基质产生的介质。骨桥蛋白和bikunin也是结晶的调节剂。暴露的肾上皮细胞常受到损伤，经历凋亡和/或坏死，引发一系列导致进一步结晶、晶体滞留和结石核心形成的事件。在草酸盐/晶体与肾细胞相互作用过程中会产生活性氧，其负责各种细胞反应。草酸钙晶体在大鼠肾脏中的沉积也会激活肾素-血管紧张素系统。草酸盐和草酸钙晶体均可选择性激活暴露的肾小管细胞中的p38丝裂原活化蛋白激酶。细胞外环境从抑制晶体成核、生长、聚集和滞留的环境转变为促进这些过程的环境。
