Lee Mi Young, Lee Eun Young, Lee Byung Jun, Won Chan Sik, Koh Jang Hyun, Shin Jang Yel, Shin Young Goo, Cho Byung Pil, Chung Choon Hee
Department of Internal Medicine, Yonsei University Wonju College of Medicine, 162 Ilsandong, Wonju, Gangwondo, Korea.
Yonsei Med J. 2007 Apr 30;48(2):301-7. doi: 10.3349/ymj.2007.48.2.301.
Diabetic nephropathy is the most serious of complications in diabetes mellitus. Thiazolidinedione (TZD) is thought to ameliorate diabetic nephropathy; however, the mechanism underlying this effect has not been elucidated. We hypothesized that the vascular endothelial growth factor (VEGF) participates in the pathogenesis of diabetic nephropathy and that TZD may be beneficial for the treatment of diabetic nephropathy because of the effect it has on VEGF.
23 Otsuka- Long-Evans-Tokushima-Fatty (OLETF) rats and eight control Long-Evans-Tokushima-Otsuka (LETO) rats were divided into the following four groups: LETO group, control OLETF group, pioglitazone treated group (10mg/ kg/day), and rosiglitazone treated group (3mg/kg/day).
A progressive increase in urinary protein excretion was observed in the diabetic rats. Glomerular VEGF expression in the control OLETF rats was significantly higher than in the control LETO rats. However, there was a significant reduction in both the glomerular VEGF expression and the VEGF mRNA levels after treatment with pioglitazone and rosiglitazone. The twenty-four hour urine protein levels were significantly decreased in both groups of the treated OLETF rats.
These results suggest that TZD may have beneficial effects on diabetic nephropathy by reducing the VEGF expression.
糖尿病肾病是糖尿病最严重的并发症。噻唑烷二酮（TZD）被认为可改善糖尿病肾病；然而，这种作用的潜在机制尚未阐明。我们推测血管内皮生长因子（VEGF）参与糖尿病肾病的发病机制，并且TZD可能因其对VEGF的作用而对糖尿病肾病的治疗有益。
将23只大冢-长-艾-德-肥（OLETF）大鼠和8只对照长-艾-德-大冢（LETO）大鼠分为以下四组：LETO组、对照OLETF组、吡格列酮治疗组（10mg/kg/天）和罗格列酮治疗组（3mg/kg/天）。
在糖尿病大鼠中观察到尿蛋白排泄逐渐增加。对照OLETF大鼠的肾小球VEGF表达明显高于对照LETO大鼠。然而，吡格列酮和罗格列酮治疗后，肾小球VEGF表达和VEGF mRNA水平均显著降低。两组接受治疗的OLETF大鼠的24小时尿蛋白水平均显著降低。
这些结果表明，TZD可能通过降低VEGF表达对糖尿病肾病产生有益作用。
