Cha Dae Ryong, Kang Young Sun, Han Sang Youb, Jee Yi Hwa, Han Kum Hyun, Han Jee Young, Kim Young Sik, Kim Nan Hee
Department of Internal Medicine, College of Medicine, Korea University, Ansan, South Korea.
J Endocrinol. 2004 Oct;183(1):183-94. doi: 10.1677/joe.1.05647.
Vascular endothelial growth factor (VEGF) has been implicated in the pathogenesis of diabetic nephropathy. We investigated serial changes of VEGF in the kidney and assessed whether glomerular and urinary VEGF levels are related to the severity of diabetic nephropathy. Furthermore, we examined the relationship between urinary VEGF levels and the urinary albumin excretion (UAE) rate in Otsuka-Long-Evans-Tokushima-Fatty (OLETF) rats. Glomerular VEGF mRNA expression and protein synthesis were evaluated by the reverse transcription-polymerase chain reaction, immunohistochemical staining and in situ hybridization. Urinary levels of VEGF were determined by enzyme-linked immunosorbent assay. UAE was significantly higher in OLETF rats than in control Long-Evans-Tokushima-Fatty (LETO) rats throughout the study period. Urinary VEGF levels were significantly higher from 25 to 37 weeks, and then gradually reduced until 55 weeks, although the levels were still higher than those in control rats. Urinary VEGF levels also showed a significant positive correlation with UAE (r=0.262, P=0.045) and serum creatinine (r=0.398, P=0.044), and were found to be independently correlated with UAE by Spearman's rank correlation. By immunohistochemical staining and in situ hybridization, VEGF was mainly detected in the podocytes in the glomeruli. Interestingly, a significant increase in VEGF mRNA expression was observed in the early period of diabetic nephropathy, and this was associated with increased urinary VEGF excretion. Thus, the overproduction of VEGF in the diabetic kidney may participate in the pathogenesis of early-stage diabetic nephropathy.
血管内皮生长因子（VEGF）与糖尿病肾病的发病机制有关。我们研究了肾脏中VEGF的系列变化，并评估肾小球和尿液中VEGF水平是否与糖尿病肾病的严重程度相关。此外，我们在大冢-朗-伊万科-德岛-肥胖（OLETF）大鼠中研究了尿液VEGF水平与尿白蛋白排泄（UAE）率之间的关系。通过逆转录-聚合酶链反应、免疫组织化学染色和原位杂交评估肾小球VEGF mRNA表达和蛋白质合成。通过酶联免疫吸附测定法测定尿液中VEGF的水平。在整个研究期间，OLETF大鼠的UAE显著高于对照长-伊万科-德岛-肥胖（LETO）大鼠。尿液VEGF水平在25至37周时显著升高，然后逐渐降低直至55周，尽管其水平仍高于对照大鼠。尿液VEGF水平还与UAE（r=0.262，P=0.045）和血清肌酐（r=0.398，P=0.044）呈显著正相关，并且通过Spearman等级相关性分析发现其与UAE独立相关。通过免疫组织化学染色和原位杂交，VEGF主要在肾小球足细胞中检测到。有趣的是，在糖尿病肾病早期观察到VEGF mRNA表达显著增加，这与尿液VEGF排泄增加有关。因此，糖尿病肾脏中VEGF的过度产生可能参与早期糖尿病肾病的发病机制。
