Amelioration of long-term renal changes in obese type 2 diabetic mice by a neutralizing vascular endothelial growth factor antibody
Amelioration of long-term renal changes in obese type 2 diabetic mice by a neutralizing vascular endothelial growth factor antibody
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DOI：
10.2337/diabetes.51.10.3090
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发表时间：
2002-10-01
期刊：
影响因子：
7.7
通讯作者：
Rasch, R
中科院分区：
文献类型：
--
作者：
Flyvbjerg, A;Dagnæs-Hansen, F;Rasch, R
2型糖尿病患者的糖尿病肾病是一种常见的并发症，与发病率和死亡率增加相关。多种生长因子和细胞因子参与了糖尿病肾病的发病机制，包括血管内皮生长因子（VEGF）。为了探讨VEGF在2型糖尿病肾脏变化中的作用，我们研究了中和鼠VEGF抗体在糖尿病db/db小鼠（肥胖2型糖尿病模型）中的肾脏作用。一组db/db小鼠用VEGF抗体治疗2个月，而另一组db/db小鼠用同种型匹配的无关IgG治疗相同的时间。第三组由非糖尿病db/+小鼠组成，用相同的同种型匹配的IgG处理2个月。与非糖尿病对照组相比，安慰剂治疗db/db小鼠的肾脏重量、肾小球体积、基底膜厚度（BMT）、总系膜体积、尿白蛋白排泄（UAE）和肌酐清除率（CrCl）显著增加。在VEGF抗体治疗的db/db小鼠中，肾脏重量、肾小球体积、BMT和UAE的增加减弱，而CrCl的增加被消除。VEGF抗体给药倾向于减少总系膜体积的扩张。在糖尿病动物中观察到这些效应，但对体重、血糖、胰岛素水平或摄食量无影响。总之，dbldb小鼠中VEGF的慢性抑制改善了在2型糖尿病中观察到的糖尿病肾脏变化。
Diabetic nephropathy in type 2 diabetic patients is a frequent complication associated with increased morbidity and mortality. Various growth factors and cytokines have been implicated in the pathogenesis of diabetic kidney disease, including vascular endothelial growth factor (VEGF). To explore a role for VEGF in renal changes in type 2 diabetes, we examined the renal effects of a neutralizing murine VEGF antibody in the diabetic db/db mouse, a model of obese type 2 diabetes. One group of db/db mice was treated for 2 months with a VEGF antibody, while another db/db group was treated for the same period With an isotype-matched irrelevant IgG. A third group consisting of nondiabetic db/+ mice was treated with the same isotype-matched IgG for 2 months. Placebo-treated db/db mice showed a pronounced increase in kidney weight, glomerular volume, basement membrane thickness (BMT), total mesangial volume, urinary albumin excretion (UAE), and creatinine clearance (CrCl) when compared with nondiabetic controls. In VEGF antibody-treated db/db mice, increases in kidney weight, glomerular volume, BMT, and UAE were attenuated, whereas the increase in CrCl was abolished. VEGF antibody administration tended to reduce expansion in total mesangial volume. These effects in diabetic animals were seen without impact on body weight, blood glucose, insulin levels, or food consumption. In conclusion, chronic inhibition of VEGF in dbldb mice ameliorates the diabetic renal changes seen in type 2 diabetes.