缬沙坦与氟伐他汀降低阿霉素肾病大鼠蛋白尿及肾组织NF-κB表达实验研究  

Effect of Valsartan and Fluvastatin on Reducting the Expression of Proteinuria and Nuclear Factor-κB(NF-κB) in Adriamycin-induced Nephrotic Rats

作　　者：张道友[1] 吴小冬[1] 崔明春[1] 杨沿浪[1] 杨利才[1] 朱新俭[1] 

机构地区：[1]皖南医学院附属弋矶山医院肾内科,安徽芜湖241001

出　　处：《中国现代医生》2011年第21期6-8,11,共4页China Modern Doctor

摘　　要：目的探讨缬沙坦与氟伐他汀对阿霉素(ADR)肾病大鼠蛋白尿及肾组织核因子κB(NF-κB)表达的影响。方法雄性SD大鼠120只,适应性喂养2周后,随机抽取18只为正常对照组(A组);另外102只制作阿霉素肾病模型。84只造模成功大鼠随机分为4组:B组为模型对照组(等容积生理盐水,n=21),C组为缬沙坦治疗组[缬沙坦3.5mg/(kg.d),n=21],D组为氟伐他汀治疗组[氟伐他汀10mg/(kg.d),n=21],E组为缬沙坦与氟伐他汀联合治疗组[缬沙坦3.5mg/(kg.d)加氟伐他汀10mg/(kg.d),n=21]。其后,分别于2、6、10周末,遵循随机化原则,按n=6分层抽取各组样本,收集24h尿液、血液及肾组织标本待测。结果与A组相比,B组、C组、D组和E组24h尿蛋白排泄、血清总胆固醇(TC)、甘油三酯(TG)浓度明显升高(P<0.01);免疫组化染色表明,NF-κB阳性积分明显升高(P<0.01);缬沙坦与氟伐他汀单用及联用尿蛋白排泄减少,血清TC、TG浓度降低(P<0.05或P<0.01),肾脏NF-κB表达降低(P<0.05或P<0.01)。结论缬沙坦与氟伐他汀可减轻阿霉素肾病大鼠蛋白尿、降低血清TG、TC浓度,降低肾脏NF-κB表达,联用时疗效更明显。提示缬沙坦与氟伐他汀至少部分通过降低NF-κB表达而减轻肾脏损害。Objective To investigate the influence effct of valsartan and fluvastatin on reducting the expression of proteinuria and nuclear factor -κ B （ NF-κ B ） in adriamycin-induced nephrotic rats. Methods Male Sprague-Dawley （ SD ） rats were randomly separated into five groups and given different therapies. Normal control group （ group A,n=18 ）. Nephrotic model was induced by tail introvenously injection of ADR （ 6.0mg/kg）. Eighty-four ADR-induced nephrotic male SD rats were randomly divided into 4 groups： model control group（group B： normal saline 3mL/d,n=21）, valsartan treatment group（group C, valsartan 3.5mg/ （kg · d ）, n=21 ） ,fluvastatin treatment group（group D, fluvastatin 10mg/ （ kg·d ）, n=21 ） and combining valsartan with fluvastatin treatment group（group E,valsartan 3.5mg/ （kg · d ）plus fluvastatin 10mg/（ kg ·d ）, n=21 ）. After the end of therapies for 2, 6, and 10 weeks, the samples of 24h urine, serum were collected and assayed （six rats were assigned randomly in every group）. The renal specimens were taken for the immunohistochemistry of nuclear transcription factor- κ B （ NF- κ B ）. Results Compared with group A, 24h urinary protein excretion, the serum levels of total cholesterol, and triglyceride were increased significantly in B, C, D,and E groups （ P 〈 0.01 ）. Treatment with either valsartan or fluvastatin or combined valsartan with fluvastatin could reduce 24h urinary protein excretion, decrease the serum levels of total cholesterol, triglyceride （ P 〈 0.05 or P 〈 0.01 ）, inhibit the expression of NF- κB in renal tissues. Conclusion valsartan and fluvastatin can decrease proteinuria, decrease serum triglyceride, total cholesterol and the expression of NF- κB in renal tissues in ADR-induced nephrotic rats. Combining valsartan with fluvastatin has superiority effects over monotherapies. These results suggest that Valsartan and fluvastatin may mediated through, at least partly, decreasing the expression of NF-κB in renal

关 键 词：阿霉素肾病 缬沙坦 氟伐他汀 核因子ΚB 

分 类 号：R587.2[医药卫生—内分泌]