缬沙坦与氟伐他汀单用及联用对阿霉素肾病大鼠血清肝细胞生长因子的影响  

Influence of valsartan and fluvastatin on hepatocyte growth factor in adriamycin-induced nephrotic rats

作　　者：吴小冬[1] 张道友[1] 崔明春[1] 杨利才[1] 杨沿浪[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

出　　处：《中国临床药理学与治疗学》2010年第3期305-309,共5页Chinese Journal of Clinical Pharmacology and Therapeutics

摘　　要：目的:探讨缬沙坦与氟伐他汀单用及联用对阿霉素肾病大鼠肝细胞生长因子(hepatocyte growth factor,HGF)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35mg.kg-1.d-1,n=21),D组为氟伐他汀治疗组(氟伐他汀10mg.kg-1.d-1,n=21),E组为缬沙坦与氟伐他汀联合治疗组(缬沙坦35mg.kg-1.d-1加氟伐他汀10mg.kg-1.d-1,n=21)。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:和A组相比,B组、C组、D组和E组24h尿蛋白排泄、血清TC、TG及HGF浓度明显升高(P<0.01);缬沙坦与氟伐他汀单用及联用能减少尿蛋白排泄,降低血清TC、TG浓度(P<0.05或P<0.01),升高血清及肾脏HGF浓度(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,升高HGF浓度,联用时疗效更明显。提示缬沙坦与氟伐他汀至少部分通过升高HGF浓度而减轻肾脏损害。AIM： To investigate the influence of valsartan alone and in combination with fluv astatin on hepalocyte growth factor （HGF） in adriamycin （ADR）-induced nephrotic rat models. METHODS： Male Sprague-Dawley（SD） rats were randomly separated into five groups and given different therapies. 18 normal rats wer as normal control group（group A,n= 18）. Ne phrotic model was induced by tail introvenously injection of ADR （ 6.0 mg/kg）. Eighty four ADR induced nephrotic male SD rats were randomly separated into 4 groups： without treat ment group（group B： normal saline, n=21）, valsartan treatment group（group C, valsartan 35 mg·kg^-1·d^-1, n= 21）, fluvastatin treatment group（group D, fluvastatin 10 mg·kg^-1·d^-1, n=21） and combined treatment group（group E, valsartan 35 mg·kg^-1·d^-1 plus fluvastatin 10 mg·kg^-1·d^-1, n=21）. After the end of the therapies for 2, 6, and 10 weeks, the samples of 24 h urine, serum were collected and assayed （six rats were assigned randomly in every group）. RESULTS： Compared with group A, 24 h urinary protein excretion, the serum levels of total cholesterol, triglyceride and HGF were in creased significantiy in group B, C, D,E （P〈 0.01）. Treatment with either valsartan or fluvastatin or combined with valsartan and fluvasta tin could reduce 24 h urinary protein excretion, reduce the serum levels of total cholesterol, tri glyceride （P〈0.05 or P〈0.01）, increase the levels of HGF in serium and renal. CONCLUSION： Valsartan and fluvastatin can decrease proteinuria, decrease serum triglyceride, total cholesterol and increase the HGF in ADR induced nephrotic rats. Combination of valsartan and fluvastatin has superiority over monothera pies on renal protection. These results suggest that valsartan and fluvastatin may mediated through, at least partly, increasing serum and renal HGF level and attenuating renal damage.

关 键 词：阿霉素肾病 缬沙坦 氟伐他汀 肝细胞 生长因子 

分 类 号：R965.2[医药卫生—药理学]