Schmid H, Lindmeier I, Schmitt H, Eissele R, Neuhaus G, Wehrmann M
Institute of Pathology, University of Tübingen, FRG.
Ren Physiol Biochem. 1993 Jul-Aug;16(4):222-32.
Cyclosporine A (15, 30 or 50 mg/kg.day) or olive oil (30 mg/kg.day) were administered orally to 32 male Sprague-Dawley rats for 12 or 24 days, or withdrawn for 24 days following 24 days of treatment. The specific activity of a lysosomal marker enzyme, N-acetyl-beta-D-glucosaminidase, was determined fluorometrically in single nephron segments microdissected from lyophilized kidney sections of these animals and of an additional 2 normal rats. The segments were classified according to their normal or reduced succinate dehydrogenase activity as detected in stained adjacent sections. In addition, urine specimens collected after 12, 24, 36, and 48 days of the experiment were tested for N-acetyl-beta-D-glucosaminidase activity. After treatment with cyclosporine A, changes in the activities of N-acetyl-beta-D-glucosaminidase were found only in the proximal tubules. In the convoluted segments with normal succinate dehydrogenase activity, the activity of N-acetyl-beta-D-glucosaminidase was 138-163%, and in those with reduced succinate dehydrogenase activity, it was unchanged or 66-83% of the control values. In the straight segments with reduced succinate dehydrogenase activity, the activity of N-acetyl-beta-D-glucosaminidase increased gradually along the medullary rays (122-214%) to the outer stripe of the outer medulla (178-263%) in comparison to the control values. In the urine specimens, the activity of N-acetyl-beta-D-glucosaminidase was increased to 148-152%. These tubular and urinary changes were similar for each dosage and treatment period. After withdrawal of cyclosporine A they were not present. The variety of alterations occurring within the lysosomes along the proximal tubules of cyclosporine-A-treated rats implies the convoluted part as the site of increased release of N-acetyl-beta-D-glucosaminidase into the urine.
将环孢素A（15、30或50毫克/千克·天）或橄榄油（30毫克/千克·天）口服给予32只雄性Sprague-Dawley大鼠，持续12天或24天，或在治疗24天后停药24天。通过荧光法测定从这些动物以及另外2只正常大鼠的冻干肾切片中显微解剖出的单个肾单位节段中溶酶体标记酶N-乙酰-β-D-氨基葡萄糖苷酶的比活性。根据在相邻染色切片中检测到的琥珀酸脱氢酶活性正常或降低情况对节段进行分类。此外，对实验第12、24、36和48天收集的尿液标本进行N-乙酰-β-D-氨基葡萄糖苷酶活性检测。用环孢素A治疗后，仅在近端小管中发现N-乙酰-β-D-氨基葡萄糖苷酶活性发生变化。在琥珀酸脱氢酶活性正常的曲段中，N-乙酰-β-D-氨基葡萄糖苷酶活性为对照值的138 - 163%，而在琥珀酸脱氢酶活性降低的曲段中，其活性未改变或为对照值的66 - 83%。与对照值相比，在琥珀酸脱氢酶活性降低的直段中，N-乙酰-β-D-氨基葡萄糖苷酶活性沿髓放线逐渐增加（122 - 214%）至外髓外带（178 - 263%）。在尿液标本中，N-乙酰-β-D-氨基葡萄糖苷酶活性增加至148 - 152%。每种剂量和治疗期的这些肾小管和尿液变化相似。停用环孢素A后，这些变化消失。环孢素A治疗的大鼠近端小管内溶酶体发生的各种改变表明，曲段是N-乙酰-β-D-氨基葡萄糖苷酶向尿液中释放增加的部位。
