Hydrocarbon-induced hyaline droplet nephropathy in male rats during senescence.
Hydrocarbon-induced hyaline droplet nephropathy in male rats during senescence.
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DOI：
10.1016/0041-008x(88)90096-8
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发表时间：
1988-11
影响因子：
3.8
通讯作者：
C.V.R. Murty;Michael J. Olson;Bhagwan D. Garg;A. Roy
中科院分区：
文献类型：
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作者：
C.V.R. Murty;Michael J. Olson;Bhagwan D. Garg;A. Roy
服用无铅汽油的雄性大鼠迅速出现肾病，其特征是近曲小管（PCT）细胞中透明液滴积聚。这种急性反应与长期暴露于完全挥发的汽油的雄性大鼠肾癌的发展有关。透明液滴的主要成分是α2u-球蛋白，这是一种源自肝脏的蛋白质，其合成速率在衰老过程中会下降。然而，目前关于雄性大鼠对碳氢化合物引起的肾病可能与年龄相关的易感性的信息很少。在未经治疗的雄性 Fischer 344 大鼠的肾脏中，随着年龄的增长，组成性透明液滴的数量逐渐减少。肾皮质匀浆电泳显示，年轻（3.5 个月大）雄性大鼠中存在一种大约 18 × 103 的蛋白质，可能是 α2u-球蛋白，而老年（26 个月大）雄性大鼠中完全不存在这种蛋白质。 RIA证实老年大鼠肾和肝α2u球蛋白的组成水平低于年轻大鼠的1.5%。无铅汽油（0.4ml/kg/天，口服，5天）导致3.5月龄雄性大鼠肾脏PCT中透明液滴积聚，并伴随肾中α2u-球蛋白含量显着增加（约两倍），而相同的治疗对26月龄大鼠则没有效果。最后，在年轻大鼠的肾皮质中，给予汽油后，溶酶体蛋白酶组织蛋白酶 B 和 D 的活性增加，这可能是对蛋白质积累的反应。然而，在 26 个月大的大鼠中，组织蛋白酶 B 的活性并未受到影响，而组织蛋白酶 D 的活性则因给予汽油而增加。因此，我们得出结论，动物年龄是碳氢化合物诱发肾病发生的重要决定因素，并且只有产生大量α2u-球蛋白的大鼠才容易发生这种病理。
Male rats administered unleaded gasoline rapidly develop nephropathy characterized by accumulation of hyaline droplets in cells of the proximal convoluted tubules (PCT). This acute response is implicated in development of renal carcinoma in male rats exposed chronically to wholly volatilized gasoline. A major constituent of hyaline droplets is α2u-globulin, a protein of hepatic origin for which the rate of synthesis declines during aging. Little information, however, is presently available on possible age-dependent susceptibility of male rats to hydrocarbon-induced nephropathy. In kidneys of untreated male Fischer 344 rats the number of constitutive hyaline droplets declined progressively with increasing age. Electrophoresis of renal cortical homogenates revealed a protein with Mrabout 18 × 103, probably α2u-globulin, in young (3.5 months old) male rats and total absence of this protein in aged (26 months old) males. RIA confirmed that constitutive levels of renal and hepatic α2u-globulin in old rats were less than 1.5% of those in young adults. Unleaded gasoline (0.4 ml/kg/day, po, 5 days) caused accumulation of hyaline droplets in renal PCT of 3.5-month-old males accompanied by a marked increase (about twofold) in the renal content of α2u-globulin, whereas the same treatment was without effect in 26-month-old rats. Finally, in the renal cortex of young rats the activities of the lysosomal proteases cathepsin B and D were increased following gasoline administration, presumably in response to protein accumulation. However, in 26-month-old rats cathepsin B activity was unaffected, while cathepsin D was increased by gasoline administration. Thus, we conclude that animal age is an important determinant in the development of hydrocarbon-induced nephropathy and only rats which produce large amounts of α2u-globulin are susceptible to development of this pathology.