【Objective】 To explore effects of valsartan on expression changes of nephrin and vascular endothelial growth factor(VEGF) in adriamycin(ADR)-induced-nephropathy rats. 【Methods】 Thirty-six rats of Sprague-Dawley were divided into two groups: the model group(n=24) and the control group(n=12). The rats in the model group were injected with a single dose of ADR(0.007 mg/g ) via tail-vein, while the rats in the control group were injected with a comparable volume of 0.9% saline. The model was successfully established when the 24 h urinary protein excretion exceeded 100 mg after ADR injection 1 week. Twenty rats were successful and then were randomly assigned to the ADR nephrosis group(n=10) and the valsartan group(n=10). The rats in the valsartan group were treated with valsartan[0.02 mg(g·d), i.g., once a day for 4 weeks, whereas the other rats were received a comparable volume of 0.9% saline. The 24 h urinary protein excretion was measured and the pathological changes of the renal tissues were observed under light microscope, Immunohistochemical and Western Blotting techniques to detect the expression of nephrin and VEGF, then analyzed the relationship of the data. 【Results】 1)The 24 h urinary protein and the expression of VEGF in the ADR nephrosis group were higher than those in the control group and valsartan group(P<0.05), and the expression of nephrin in the ADR nephrosis group was lower than those in the control group and valsartan group(P<0.05);2)Nephrin was negatively correlated with the 24 h urinary protein, while VEGF was positively correlated with the 24 h urinary protein. 【Conclusions】 1)Nephrin and VEGF play an important role in the pathogenesis of ADR nephrosis. 2)Valsartan decreases the urine albumin excretory rate in rats with ADR nephrosis, which mechanism may be at least partly correlated with enhancing the expression of nephrin and inhibiting the expression of VEGF in kidney.
Key words
vascular endothelial growth factor /
valsartan /
adriamycin nephrosis /
proteinuria /
nephrin
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References
[1] Kestila M, Lenkkeri U, Mannikko M, et al. Positionally cloned gene for a novel glomerular protein nephrin is mutated in congenital nephrotic syndrome[J]. Mol Cell,1998,1(4):575-582.
[2] Flyvbjerg A, Hansen FD, de Vriese AS, et al. Amelioration of longterm renal changes in obese type 2 diabetic mice by a neutralizing vascular endothelial growth factor antibody[J]. Diabetes,2002,51(10):3090-3094.
[3] Kathryn E, White RW. Bilous on behalf of the Diabiopsies stuely Group. Structural alterations to the podocyte are related to proteinuria in 2 diabetic patients[J]. Nephrol Dial Transplant,2004,19(6):1437-1440.
[4] 唐万欣,陈泽君,黄颂敏,等.缬沙坦对糖尿病鼠肾血管内皮生长因子及其受体Flk-1的影响[J].四川大学学报:医学版,2008,29(3):223-226.
[5] Jalako H. Pathogenesis of proteinuria:lessons learned from nephrin and podocin[J]. Pediatr Nephrol,2003,18(6):487-491.
[6] Kawachi H, Koike H, Shimizu F. Molecular structure and function of the slit diaphragm: expression of nephrin in proteinuric states and in developing glomeruli[J]. Nephrol Dial Transplant,2002,17(S19):20-22.
[7] Kestila M, Lenkkeri U, Mannikko M, et al. Positionally cloned gene for a novel glomerular protein-nephrin-is mutated in congenital nephritic syndrome[J]. Mol Cell,1998,1(4):575-582.
[8] Hauser PV, Collino F, Bussolati B, et al. Nephrin and endothelial injury[J]. Curr Opin Nephrol Hypertens,2009,18(1):3-8.
[9] Tryggvason K, Patrakka J, Wartiovaara J. Hereditary proteinuria syndromes and mechanisms of proteinuria[J]. N Engl J Med,2006,354(13):1387-1401.
[10] 杨维娜,于琳华,钱亦华,等.阿霉素肾病大鼠模型动态变化及其足细胞数量和nephrin的表达变化[J].中山大学学报:医学科学版,2009,30(5):512-516.
[11] 彭亚琴,莫樱,蒋小云,等.阿霉素肾病大鼠肾组织中nephrin和CD2AP的表达及意义[J]. 中山大学学报:医学科学版,2009,30(1):15-20.
[12] Dong YF, Liu L, Lai ZF, et al. Aliskiren enhances protective effects of valsartan against type 2 diabetic nephropathy in mice[J]. J Hypertens,2010,28(7):1554-1565.
[13] Zhang Y, Chen B, Hou XH, et al. Effects of mycophenolate mofetil, valsartan and their combined therapy on preventing podocyte loss in early stage of diabetic nephropathy in rats[J]. Chin Med J,2007,120(11):988-995.
[14] 杨维娜,任淑婷,钱亦华,等.阿霉素肾病大鼠肾小球中足细胞数量及nephrin、VEGF的表达变化[J].四川大学学报:医学版,2010,41(3):458-462.
[15] Eremina V, Sood M, Haigh J, et al. Glomerular-specific alterations of VEGF-A expression lead to distinct congenital and acquired renal diseases[J]. J Clin Invest,2003,111(5):707-716.
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