Montenez J P, Kishore B K, Maldague P, Tulkens P M
Unité de Pharmacologie Cellulaire et Moléculaire, Université Catholique de Louvain, Brussels, Belgium.
Toxicol Lett. 1994 Sep;73(3):201-8. doi: 10.1016/0378-4274(94)90059-0.
Aminoglycoside antibiotics, such as gentamicin, cause an early lysosomal phospholipidosis in the renal cortex, which is considered as a key event in the onset of acute tubular necrosis induced by these drugs. In a model of primary cultures of embryonic rat fibroblasts which develop typical lysosomal phospholipidosis when incubated with gentamicin (decrease of sphingomyelinase activity; increase in total cells lipid phosphorus; appearance of so-called 'myeloid bodies' in lysosomes), we observed a protective effect exerted by inhibitors of cysteine proteinases (leupeptin, E-64) against this alteration on the basis of both biochemical and morphological criteria. Actually leupeptin and E-64 caused a marked stimulation of sphingomyelinase activity both in control and in gentamicin-treated cells, which we suggest to be the cause of protection.
氨基糖苷类抗生素，如庆大霉素，可导致肾皮质早期溶酶体磷脂沉积症，这被认为是这些药物诱发急性肾小管坏死起始过程中的关键事件。在胚胎大鼠成纤维细胞原代培养模型中，当与庆大霉素一起孵育时会出现典型的溶酶体磷脂沉积症（鞘磷脂酶活性降低；总细胞脂质磷增加；溶酶体中出现所谓的“髓样小体”），基于生化和形态学标准，我们观察到半胱氨酸蛋白酶抑制剂（亮抑酶肽、E-64）对这种改变具有保护作用。实际上，亮抑酶肽和E-64在对照细胞和经庆大霉素处理的细胞中均引起鞘磷脂酶活性的显著刺激，我们认为这是产生保护作用的原因。
