Study on the Effect of the Long Term Administration of Germanium (IV) Oxide on Rat Kidney.

长期服用氧化锗(IV)对大鼠肾脏影响的研究。

• 批准号: 07670396
• 负责人: YAMAZAKI Nobuyuki
• 金额: $ 1.6万
• 依托单位: University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1996
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07670396/
• 关键词: Germanium (IV) oxide; Interstitial nephritis; ED1 positive cell; Collagen type IV; Fibronectin; L-arginine; Enalapril; 酸化ゲルマニウム(IV); 二酸化ゲルマニウム; ゲルマニウム中毒; マクロフア-ジ; フイブロネクチン

In this study, we investigated the chronic nephrotoxicity of germanium (IV) oxide (GeO_2) in rat and the preventive effects of drugs (enalapril and L-arginine) on the progression of GeO_2 indced nephropathy. Twenty female Wistar rats were fed a standard rat chow containing 1500ppm GeO_2 for 5 months (GeO_2 group). Ten control rats were fed a standard rat chow. At the end of month 4, two rats in the GeO_2 group and one control rat were killed and confirmed the induction of tubulointerstitial nephritis by light microscopy. Then each group was divided into 3 groups. One group was given tap water without a change. Other two groups were administered 50ppm enalapril or 1% L-agrinine solution as a drinking water for last 3 weeks of the experimental period. Rats given GeO_2 had significantly lower weight and significantly higher BUN than rats not given GeO_2. By light microscopic examination, expansion of renal interstitium caused by degeneration and necrosis of tubular epithelium was observed in all rats given GeO_2. Infiltration by inflammatory cells in interstitium was also evident in the GeO_2 group. Rats in the GeO_2 group given tap water was observed the accumulation of the ED1 positive cells (macrophage) and the increased expression of the extracellular matrices (collagen typeIV and fibronectin) in interstitium by immunohistochemistry. Administration of L-arginine for 3 weeks markedly decreased the accumulation of the ED1 positive cells and the expression of the extracellular matrices in renal interstitium of GeO_2 rats compared with similar rats given tap water. But enalapril had little effect on those changes. Relative expression levels of collagen typeIV mRNA in kidney were measred by RT-PCR.The levels of mRNA correlated with that of collagen typeIV.The increase of the mRNA level in rats given GeO_2 was suppressed by the administration of L-arginine significantly.

本研究观察了氧化锗(GeO_2)对大鼠的慢性肾毒性及药物(依那普利和L-精氨酸)对GeO_2肾病的预防作用。雌性Wistar大鼠20只，喂饲含1500 ppm GeO_2的标准饲料5个月(GeO_2组)。给10只对照组大鼠喂食标准的大鼠饲料。4个月末，GeO_2组2只大鼠和对照组1只大鼠处死，光镜下证实肾小管间质肾炎的发生。然后每组又分成3组。其中一组在没有变化的情况下给了自来水。另两组分别给予50ppm依那普利或1%L-麦角碱溶液作为饮用水，试验期最后3周。给GeO_2的大鼠体重显著低于未给GeO_2的大鼠，BUN显著高于未给GeO_2的大鼠。光镜下可见所有给GeO_2的大鼠肾间质均因肾小管上皮细胞变性、坏死而扩张，间质有明显的炎性细胞浸润。免疫组织化学方法观察饮用自来水的GeO2组大鼠肾间质ED1阳性细胞(巨噬细胞)聚集，细胞外基质(IV型胶原和纤维连接蛋白)表达增加。L精氨酸给药3周后，GeO2大鼠肾间质ED1阳性细胞积聚明显减少，细胞外基质表达明显减少。但依那普利对这些变化几乎没有影响。逆转录聚合酶链式反应检测肾脏IV型胶原基因的相对表达水平，其表达水平与IV型胶原基因表达水平呈正相关。L精氨酸可显著抑制GeO2组大鼠肾脏IV型胶原基因表达水平的升高。

项目成果

山崎信行,他: "二酸化ゲルマニウムによる間質性腎炎の発症とその進展に及ぼすエナラプリル、L-アルギニンの影響" 日本衛生学雑誌. 51(1). 350-350 (1996)

Nobuyuki Yamazaki 等人：“依那普利和 L-精氨酸对二氧化锗诱导的间质性肾炎的发病和进展的影响”日本卫生杂志 51(1) (1996)。

Yamazaki, N.et al.: "Germanim dioxide induced interstitial nephropathy in rat and the preventive effects of enalapril of L-arginine on the progression of the disease." Jpn. J.Hyg.51 (1). 350 (1996)

Yamazaki, N.等人：“二氧化锗诱发大鼠间质性肾病，以及 L-精氨酸依那普利对疾病进展的预防作用。”