【目的】 探讨nephrin、血管内皮生长因子(vascular endothelial growth factor, VEGF)在阿霉素肾病大鼠肾小球中的表达变化及缬沙坦对其影响。 【方法】 SD大鼠36只随机分为两组,模型组24只和对照组12只。模型组大鼠尾静脉一次注射盐酸阿霉素(adriamycin, ADR)0.007 mg/g,对照组大鼠尾静脉注射等容积生理盐水,注射ADR 1周后尿蛋白定量>100 mg/24 h即算建模成功,共有20只大鼠建模成功,随机又分为肾病模型组和缬沙坦干预组,每组10只。缬沙坦干预组给予缬沙坦0.02 mg/(g·d)灌胃,1次/d,共4周。对照组和肾病模型组给予等容积生理盐水灌胃。实验结束后检测各组大鼠24 h尿蛋白定量,光镜观察肾脏病理学改变,免疫组化技术和Western Blotting技术检测nephrin、VEGF的表达,并分析数据相关性。 【结果】 1)肾病模型组及缬沙坦干预组24 h尿蛋白定量、肾小球VEGF表达均高于对照组(P<0.05),但缬沙坦干预组上述指标均低于肾病模型组(P<0.05)。肾病模型组及缬沙坦干预组肾小球nephrin表达低于对照组(P<0.05),但缬沙坦干预组nephrin表达高于肾病模型组(P<0.05);2)nephrin的表达与24 h尿蛋白定量呈负相关关系;VEGF的表达与24 h尿蛋白定量呈正相关关系。 【结论】 1)Nephrin及VEGF在阿霉素肾病发病机制中起重要作用;2)缬沙坦可减少阿霉素肾病大鼠尿蛋白的排出,其机制可能与增加nephrin的表达及减少VEGF的表达有关。
Abstract
【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.
关键词
阿霉素肾病 /
蛋白尿 /
nephrin /
血管内皮生长因子 /
缬沙坦
Key words
vascular endothelial growth factor /
valsartan /
adriamycin nephrosis /
proteinuria /
nephrin
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参考文献
[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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