Shibasaki T, Nakano H, Ohno I, Ishimoto F, Sakai O
Second Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan.
Biol Trace Elem Res. 1993 May-Jun;37(2-3):261-7. doi: 10.1007/BF02783800.
We produced an animal model of CdCl2 nephrotoxicity in rats, and treated them with polyaspartic acid (PAA) to prevent renal damage. Male Sprague-Dawley (SD) rats (190-200 g) were used to induce proximal renal tubular damage by daily injection of CdCl2 3.0 mg/1,000 g body wt for 2 wk. CdCl2-exposed SD rats exhibited significant increases in urine volume, urinary excretion of N-acetyl-beta-D-glucosaminidase (NAG), alanine aminopeptidase (AAP), and fractional excretion of sodium (FENa) and a decrease in the percentage of tubular reabsorption of phosphate (%TRP). Of these indicators of proximal tubular function, AAP and %TRP are more sensitive than NAG or FENa. No glycosuria or aminoaciduria, however, were observed. PAA markedly improved these indicators of proximal tubular function. Daily urinary protein excretion and creatinine clearance, on the other hand, did not change after administration of PAA. Cd concentrations in the cortex were 3 times higher than in the medulla, however, there were no differences between Cd-treated rats and PAA-treated rats. Our animal model is an excellent one for determining the effect of cadmium on renal proximal tubule damage. PAA appears to be useful in the treatment of CdCl2 nephrotoxicity.
我们建立了大鼠氯化镉肾毒性动物模型,并用聚天冬氨酸(PAA)对其进行治疗以预防肾损伤。选用雄性Sprague-Dawley(SD)大鼠(体重190 - 200 g),通过每天注射3.0 mg/1000 g体重的氯化镉,连续注射2周来诱导近端肾小管损伤。暴露于氯化镉的SD大鼠尿量、N - 乙酰 - β - D - 氨基葡萄糖苷酶(NAG)、丙氨酸氨基肽酶(AAP)的尿排泄量、钠分数排泄率(FENa)显著增加,而磷酸盐肾小管重吸收百分比(%TRP)降低。在这些近端肾小管功能指标中,AAP和%TRP比NAG或FENa更敏感。然而,未观察到糖尿或氨基酸尿。PAA显著改善了这些近端肾小管功能指标。另一方面,给予PAA后,每日尿蛋白排泄量和肌酐清除率没有变化。皮质中的镉浓度比髓质高3倍,然而,氯化镉处理的大鼠和PAA处理的大鼠之间没有差异。我们的动物模型是确定镉对肾近端小管损伤影响的优良模型。PAA似乎对治疗氯化镉肾毒性有用。