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

本研究探讨了氧化锗（GeO_2）对大鼠的慢性肾毒性，以及依那普利和l -精氨酸对氧化锗（GeO_2）肾病的预防作用。雌性Wistar大鼠20只，连续5个月饲喂含1500ppm GeO_2的标准鼠粮（GeO_2组）。10只对照大鼠喂食标准鼠粮。第4月末，取2只大鼠和1只对照大鼠，在光镜下证实其诱导肾小管间质性肾炎。然后每组分为3组。其中一组只喝自来水，没有任何变化。另外两组在实验最后3周给予50ppm依那普利或1% L-agrinine溶液作为饮用水。注射GeO_2的大鼠体重显著低于未注射GeO_2的大鼠，BUN显著高于未注射GeO_2的大鼠。光镜下观察，注射GeO_2大鼠肾小管上皮变性坏死引起肾间质扩张。GeO_2组间质有明显的炎性细胞浸润。用免疫组化方法观察自来水注射GeO_2组大鼠间质中ED1阳性细胞（巨噬细胞）的积累和细胞外基质（iv型胶原和纤维连接蛋白）表达的增加。l -精氨酸给药3周后，ge_2大鼠肾间质中ED1阳性细胞的积累和细胞外基质的表达均明显低于自来水大鼠。但依那普利对这些变化几乎没有影响。采用RT-PCR检测肾组织ⅳ型胶原mRNA的相对表达量。mRNA水平与iv型胶原蛋白水平相关。l -精氨酸能明显抑制大鼠注射GeO_2后mRNA水平的升高。

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.