中文摘要：

目的研究阿霉素肾病大鼠肾组织中表皮生长因子（EGF）及其受体EGFR的表达分布以及表达量与尿蛋白之间关系。方法选择第5天、14天、28天作为动态观察的时点，同期设立正常对照。采用荧光定量RT-PCR、免疫组织化学及计算机图像定量分析EGF mRNA以及EGF、EGFR蛋白在肾组织的表达，同时测定24h尿蛋白定量。WT1和EGFR双重免疫组化确定EGFR在肾小球内确切细胞定位。结果阿霉素注射后第5天，EGFmRNA即较正常增高，28d明显增高并高于5d和14d。正常对照组EGF阳性细胞主要分布于远曲小管和髓袢，阿霉素组EGF还在集合管和近曲小管上表达；EGF阳性表达范围和强度随尿蛋白增加而增加；EGFmRNA表达量以及EGF在肾小管中的表达强度与24h尿蛋白量呈正相关。肾小管上皮细胞广泛表达EGFR，阿霉素组EGFR在小管表达均高于正常，但组间各时点差异无显著性；随尿蛋白增加EGFR在肾小球内表达逐渐增多。EGFR在肾小球和肾小管中的表达强度均与24h尿蛋白量呈正相关。WT1和EGFR双重免疫组化显示阿霉素肾病组EGFR可在足突细胞上表达，正常组则无。结论阿霉素肾病大鼠的肾小球脏层上皮有EGFR的表达。EGF／EGFR可能参与了阿霉素肾病的发病过程以及蛋白尿的形成。

英文摘要：

Objeective To explore the distribution and expression of renal epidermal growth factor （EGF） and its receptor EGFR in rats with adriamycin nephrosis, and to reveal the possible correlation of expression of EGF and EGFR with the development of proteinuria. Methods We selected 5 days, 14 days, 28 days as three study points after adriamycin injection. The expression of EGFR and EGFmRNA and protein was detected by real-time quantitative RT-PCR, immunohistochemical staining and computer image analysis. Double-immunohistochemical staining was used to confirm the location of EGFR in glomeruli. Results At 5th day the expression level of EGFmRNA was higher than that of control group （ P 〈 0.01 ）. In the adriamycin group, the expression level of EGFmRNA at 28th day was much higher than that at 5th and 14th day （ P 〈 0.01 ）. The distribution of EGF was primarily along distal convoluted tubule and Henle＇ s loop in control rats, whereas in nephrosis rat proximal convoluted tubules and collecting ducts showed EGF distribution as well. Accompanying with the augment of proteinuria level, the intensity and scope of EGF staining increased ; the expression level of EGFmRNA and the intensity of EGF staining along renal tubules were positively correlated with 24 hours proteinuria level （r = 0.608, P = 0.001; r = 0.887, P = 0.000）. EGFR staining was widely distributed in renal tubular epithelia cells. The intensity and area of EGFR staining along renal tubules in nephrosis group was higher than that in control group（ P 〈 0.01 ）, however in nephrosis group there was no statistical significant difference among various study points, namely 5th, 14th and 28th day （P 〉 0.05 ）. The glomenllar positive staining of EGFR increased accompanying the augment of proteinuria level（ P 〈 0.01 ）. The intensity of EGFR staining along glomeruli and renal tubuleswas positively correlated with 24 hours proteinuria level （r = 0.884, P = 0.000; r = 0.70, P = 0.001 ）. Doublemmunohistochemical staining of WT1 and EG