Asan E, Kugler P
Histochemistry. 1985;82(1):81-92. doi: 10.1007/BF00502094.
The effects of maleate on membrane-bound and lysosomal peptidases were studied histochemically in the kidney and biochemically in the kidney and the urine of male and female rats 6 h after the administration of two different doses of sodium maleate (150 and 300 mg/kg body weight). Additionally, the proteinuria of experimental animals was electrophoretically analysed to detect maleate-induced alterations in the urinary protein composition. The histochemistry of the brush-border peptidases (aminopeptidase A, gamma-glutamyltransferase) showed dose-dependent maleate effects in the late pars convoluta and the pars recta of the proximal tubule (blurring of the brush-border enzyme reaction pattern). The female animals were more severely affected by both maleate doses. After maleate treatment, enzyme-activity measurements in the kidney homogenate supernatant and urine indicated dose-dependent structural destruction of the proximal tubule, especially of brush-border membranes, and revealed an increase in enzyme excretion. Both the maleate-induced enzyme excretion and proteinuria were more pronouncedly increased in females than in males. Electrophoretic analysis of urinary proteins revealed alterations in the urinary-protein composition after maleate treatment, which favoured the excretion of proteins with a molecular weight higher than 20,000 daltons. Again, sex-related differences in the maleate effects were demonstrated. The results indicate that maleate causes alterations in the brush-border membranes and, especially at higher doses, results in cellular destruction selectively in the late proximal tubule of rat kidneys. Selectivity was also encountered in the maleate effects on urinary-protein composition, suggesting that the tubular alterations lead to an inhibition of the reabsorption of mainly high-molecular-weight proteins. Although the nature of the effects was independent of sex, it appears that females are less well protected against tubular damage caused by maleate.
在给雄性和雌性大鼠分别注射两种不同剂量（150和300mg/kg体重）的马来酸钠6小时后，采用组织化学方法研究了马来酸盐对肾脏中膜结合肽酶和溶酶体肽酶的影响，并采用生物化学方法研究了其对肾脏和尿液的影响。此外，对实验动物的蛋白尿进行了电泳分析，以检测马来酸盐引起的尿蛋白组成变化。刷状缘肽酶（氨肽酶A、γ-谷氨酰转移酶）的组织化学显示，在近端小管的曲部晚期和直部，马来酸盐的作用呈剂量依赖性（刷状缘酶反应模式模糊）。两种剂量的马来酸盐对雌性动物的影响更严重。马来酸盐处理后，肾脏匀浆上清液和尿液中的酶活性测量表明，近端小管尤其是刷状缘膜出现了剂量依赖性的结构破坏，并显示酶排泄增加。马来酸盐诱导的酶排泄和蛋白尿在雌性中比在雄性中增加得更明显。尿蛋白的电泳分析显示，马来酸盐处理后尿蛋白组成发生了变化，有利于分子量高于20,000道尔顿的蛋白质排泄。同样，马来酸盐作用存在性别差异。结果表明，马来酸盐会导致刷状缘膜发生改变，尤其是在高剂量时，会选择性地导致大鼠肾脏近端小管晚期的细胞破坏。马来酸盐对尿蛋白组成的影响也具有选择性，这表明肾小管改变导致主要高分子量蛋白质的重吸收受到抑制。虽然这种作用的性质与性别无关，但似乎雌性对马来酸盐引起的肾小管损伤的保护作用较弱。
