Vascular endothelial growth factor is increased during early stage of diabetic nephropathy in type II diabetic rats
Vascular endothelial growth factor is increased during early stage of diabetic nephropathy in type II diabetic rats
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DOI：
10.1677/joe.1.05647
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发表时间：
2004-10-01
影响因子：
4
通讯作者：
Kim, NH
中科院分区：
文献类型：
--
作者：
Cha, DR;Kang, YS;Kim, NH
血管内皮生长因子（VEGF）参与了糖尿病肾病的发病机制。我们研究了VEGF在肾脏中的一系列变化，并评估了肾小球和尿液VEGF水平是否与糖尿病肾病的严重程度相关。此外，我们研究了大冢长埃文斯德岛脂肪（OLETF）大鼠尿VEGF水平和尿白蛋白排泄率（UAE）之间的关系。采用逆转录-聚合酶链反应、免疫组化和原位杂交检测肾小球VEGF mRNA表达和蛋白合成。采用酶联免疫吸附法测定尿VEGF水平。在整个研究期间，OLETF大鼠的UAE显著高于对照Long-Evans-Tokushima-Fatty（LETO）大鼠。尿VEGF水平从25到37周显著升高，然后逐渐降低，直到55周，尽管水平仍然高于对照组大鼠。尿VEGF水平与UAE（r=0.262，P=0.045）和血肌酐（r=0.398，P=0.044）呈显著正相关，斯皮尔曼等级相关分析显示，尿VEGF水平与UAE独立相关。免疫组织化学染色和原位杂交显示VEGF主要表达于肾小球足细胞。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VEGF排泄增加有关。因此，VEGF在糖尿病肾脏中的过度产生可能参与早期糖尿病肾病的发病机制。
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.