Stonard M D, Gore C W, Oliver G J, Smith I K
Central Toxicology Laboratory, Imperial Chemical Industries, Macclesfield, Cheshire, UK.
Fundam Appl Toxicol. 1987 Aug;9(2):339-51. doi: 10.1016/0272-0590(87)90056-x.
Acute experimental models of renal damage to the proximal tubular, glomerular, and papillary regions of the rat were produced by administration of hexachloro-1:3-butadiene (HCBD), puromycin aminonucleoside (PAN), and 2-bromoethylamine (BEA), respectively. Several routine indicators of nephrotoxicity, the enzymes alkaline phosphatase and N-acetyl-beta-glucosaminidase, and the molecular weight of protein excretion were determined on urine samples. Tubular damage produced by HCBD or BEA was discriminated both quantitatively and qualitatively from glomerular damage produced by PAN. The latter was characterized by a pronounced increase in protein excretion, especially proteins with molecular weight greater than 40,000 Da. In contrast, protein excretion in tubular damage was raised only slightly and characterized by excretion of proteins of a wide range of molecular weights. Proximal tubular damage caused by HCBD and papillary damage caused by BEA were distinguished both by conventional urinalysis (volume and specific gravity) and by measurement of the two urinary enzymes. Alkaline phosphatase and glucose were markedly and transiently elevated in proximal tubular damage and N-acetyl-beta-glucosaminidase showed a sustained elevation in papillary damage. It is concluded that both selective urinary enzymes and the molecular weight pattern of urinary proteins can be used to provide diagnostic information about the possible site of renal damage.
分别通过给予六氯 - 1:3 - 丁二烯（HCBD）、嘌呤霉素氨基核苷（PAN）和2 - 溴乙胺（BEA），建立了大鼠近端肾小管、肾小球和乳头区肾损伤的急性实验模型。对尿样测定了几种肾毒性常规指标、碱性磷酸酶和N - 乙酰 - β - 氨基葡萄糖苷酶这两种酶以及蛋白质排泄的分子量。由HCBD或BEA引起的肾小管损伤在定量和定性上都与由PAN引起的肾小球损伤有所区别。后者的特征是蛋白质排泄显著增加，尤其是分子量大于40,000 Da的蛋白质。相比之下，肾小管损伤时蛋白质排泄仅略有升高，且其特征是排泄多种分子量的蛋白质。由HCBD引起的近端肾小管损伤和由BEA引起的乳头区损伤，通过传统尿液分析（尿量和比重）以及两种尿酶的测定得以区分。在近端肾小管损伤中，碱性磷酸酶和葡萄糖显著且短暂升高，而在乳头区损伤中，N - 乙酰 - β - 氨基葡萄糖苷酶持续升高。得出的结论是，选择性尿酶和尿蛋白的分子量模式均可用于提供有关肾损伤可能部位的诊断信息。
