›› 2009, Vol. 29 ›› Issue (9): 1040-.

• Original article (Basic research) • Previous Articles     Next Articles

Effects of rapamycin on nephropathy of diabetic rats and expressions of vascular endothelial growth factor and its receptor

XIAO Li-fang, GU Le-yi, LIANG Xin-yue, WANG Li-hua, ZHANG Min-fang, QIAN Jia-qi, NI Zhao-hui, DAI Hui-li, YAN Yu-cheng   

  1. Department of Nephrology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200127, China
  • Online:2009-09-25 Published:2009-09-29
  • Supported by:

    Major Foundamental Research Program of Shanghai Committee of Science and Technology, 07JC14037


Objective To elucidate the role of vascular endothelial growth factor (VEGF) in the pathogenesis of diabetic nephropathy by investigating the effect of rapamycin on the kidney in experimental diabetic rats. Methods Diabetic rat models were established by intraperitoneal injection of streptozotocin (65 mg/kg). Twelve weeks later, all the 27 rat models were divided into rapamycin treatment group (treated by rapamycin for 4 weeks, n=9), angiotensin Ⅱ receptor antagonist, L-158809, treatment group (positive control group, treated by L-158809 for 4 weeks, n=5), and diabetic nephropathy group (intragastric administration of same amount of saline for 4 weeks, n=9). Another 9 normal SD rats were as normal control group. Blood, urine, and renal tissue samples were collected for determining changes of glomerular structure and function. Expressions of VEGF and VEGF receptor 2 (VEGFR2) in renal tissues were investigated by Western blotting and immunohistochemistry. Results Compared with normal control group, the 24 h urinary albumin increased; creatinine clearance rate rose; glomerular volume increased; and glomerular basement membrane thickened in diabetic nephropathy (P<0.01). Compared with diabetic nephropathy group, the 24 h urinary albumin decreased, and glomerular volume and glomerular basement membrane were almost same in rapamycin treatment group and positive control group. The expressions of VEGF and VEGFR2 in diabetic nephropathy group were higher than those in normal control group (P<0.01). The expressions of VEGF and VEGFR2 in rapamycin treatment group and positive control group were lower than those in diabetic nephropathy group (P<0.01). Conclusion Rapamycin can slow the progression of diabetic nephropathy by ameliorating the albuminuria and renal hypertrophy, preventing thickness of glomerular basement membrane, and reducing the expressions of VEGF and VEGR2.

Key words: diabetic nephropathy, rapamycin, vascular endothelial cell growth factor, vascular endothelial cell growth factor receptor

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