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大鼠尿液和血清中β2-微球蛋白的测定。II. 其尿样测定在特定肾毒性模型中的应用。

Determination of rat beta 2-microglobulin in urine and in serum. II. Application of its urinary measurement to selected nephrotoxicity models.

作者信息

Viau C, Bernard A, Ouled A, Lauwerys R

出版信息

J Appl Toxicol. 1986 Jun;6(3):191-5. doi: 10.1002/jat.2550060310.

Abstract

beta 2-microglobulin (beta 2-m) was measured in the urine of rats by a specific immunoassay based on latex particles agglutination. The excretion of this protein was compared to the excretion of the enzyme beta-N-acetyl-D-glucosaminidase (NAG), albumin and amino acids in rats treated with either a single dose of sodium chromate (5 and 10 mg kg-1), repeated doses of gentamicin (5 and 20 mg kg-1), or cadmium (1 mg kg-1), and in aging rats (from 2 to 20 months). All treatments resulted in an early increased excretion of beta 2-m indicative of functional alterations of the proximal tubular cells. An increased NAG excretion was observed only at the highest dose of chromate and in the cadmium model but the relative increases of beta 2-m were much larger (up to 200 times the control values against four times the control values for NAG). From 2 to 20 months of age, urinary beta 2-m increases by a factor of four. Aminoacids excretion showed little sensitivity in the various models. Albumin showed little variations in purely tubular or in the tubular phase of renal injury but the chronic progressive nephrosis of aging rats caused a 40-fold increase in its excretion between 2 and 20 months of age. Therefore urinary beta 2-m, albumin and albumin/beta 2-m ratio provide useful tools in the assessment of nephrotoxicity and of its mechanisms in various experimental models.

摘要

采用基于乳胶颗粒凝集的特异性免疫分析法测定大鼠尿液中的β2-微球蛋白(β2-m)。将该蛋白的排泄情况与用单剂量铬酸钠(5和10mg/kg)、重复剂量庆大霉素(5和20mg/kg)或镉(1mg/kg)处理的大鼠以及衰老大鼠(2至20个月)中β-N-乙酰-D-氨基葡萄糖苷酶(NAG)、白蛋白和氨基酸的排泄情况进行比较。所有处理均导致β2-m排泄早期增加,表明近端肾小管细胞功能改变。仅在铬酸钠最高剂量组和镉模型中观察到NAG排泄增加,但β2-m的相对增加幅度要大得多(高达对照值的200倍,而NAG为对照值的四倍)。从2至20个月龄,尿β2-m增加了四倍。在各种模型中,氨基酸排泄的敏感性较低。在单纯肾小管损伤或肾损伤的肾小管期,白蛋白变化不大,但衰老大鼠的慢性进行性肾病导致其在2至20个月龄时排泄增加40倍。因此,尿β2-m、白蛋白和白蛋白/β2-m比值为评估各种实验模型中的肾毒性及其机制提供了有用的工具。

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