Uriu K, Kaizu K, Qie Y L, Ito A, Takagi I, Suzuka K, Inada Y, Hashimoto O, Eto S
Kidney Center, First Department of Internal Medicine, University of Occupational and Environmental Health School of Medicine, Kitakyushu, Japan.
Toxicol Appl Pharmacol. 2000 Dec 1;169(2):151-8. doi: 10.1006/taap.2000.9063.
Our study was designed to clarify whether renal functional reserve (RFR) was impaired in rats chronically treated with oral low-dose cadmium (Cd). Rats (n = 15) were treated with 1 ppm of cadmium chloride added to drinking water. We measured RFR (representing the ability to increase glomerular filtration rate [GFR] and renal plasma flow [RPF] in response to infusion of glycine) at 2 and 10 months after initiation of exposure to Cd. Urinary excretion of Cd was significantly higher in 10-month Cd-treated rats than in age-matched control rats (provided with distilled water only). Weight gain was noted in Cd-treated rats, which was identical to that in age-matched control rats. Urinary volume and urinary excretions of sodium, protein, and glucose were similar in the two groups. There were no differences in the basal mean arterial pressure (MAP) and renal hemodynamics between 2-month Cd-treated and age-matched control rats. Infusion of glycine resulted in significant increases in GFR and RPF and a significant reduction in renal vascular resistance (RVR) in both 2-month Cd-treated and age-matched control rats (control, GFR: 133 +/- 10%, RPF: 148 +/- 8%; 2-month Cd-treated rats, GFR: 152 +/- 12% and RPF: 154 +/- 7%). The basal MAP and renal hemodynamics in 10-month Cd-treated rats were also identical to those in age-matched control rats. Infusion of glycine significantly increased GFR in 10-month control rats (132 +/- 15%), but not in 10-month Cd-treated rats (98 +/- 11%), but did not change MAP, RPF, and RVR in both groups. In addition to age-related pathological changes, mild renal interstitial edema and degenerative mitochondria with diminished matrix density and loss of the cristae in the proximal tubular cells were more frequent in 10-month Cd-treated rats. Our results suggest that long-term oral intake of low-dose Cd in rats exacerbate age-related impairment of renal functional reserve and degeneration of the proximal tubular epithelial cells.
我们的研究旨在阐明长期口服低剂量镉（Cd）的大鼠肾功能储备（RFR）是否受损。将15只大鼠用添加到饮用水中的1 ppm氯化镉进行处理。在开始接触Cd后2个月和10个月时，我们测量了RFR（代表对输注甘氨酸作出反应增加肾小球滤过率[GFR]和肾血浆流量[RPF]的能力）。10个月大的Cd处理大鼠的尿镉排泄量显著高于年龄匹配的对照大鼠（仅提供蒸馏水）。Cd处理大鼠体重增加，与年龄匹配的对照大鼠相同。两组的尿量以及钠、蛋白质和葡萄糖的尿排泄量相似。2个月大的Cd处理大鼠与年龄匹配的对照大鼠之间的基础平均动脉压（MAP）和肾血流动力学没有差异。在2个月大的Cd处理大鼠和年龄匹配的对照大鼠中，输注甘氨酸均导致GFR和RPF显著增加以及肾血管阻力（RVR）显著降低（对照组，GFR：133±10%，RPF：148±8%；2个月大的Cd处理大鼠，GFR：152±12%，RPF：154±7%）。10个月大的Cd处理大鼠的基础MAP和肾血流动力学也与年龄匹配的对照大鼠相同。输注甘氨酸使10个月大的对照大鼠的GFR显著增加（132±15%），但10个月大的Cd处理大鼠未增加（98±11%），且两组的MAP、RPF和RVR均未改变。除了与年龄相关的病理变化外，10个月大的Cd处理大鼠更频繁地出现轻度肾间质水肿以及近端肾小管细胞中线粒体退行性变，基质密度降低且嵴消失。我们的结果表明，大鼠长期口服低剂量Cd会加剧与年龄相关的肾功能储备损害以及近端肾小管上皮细胞的退变。
