苯那普利及己酮可可碱对阿霉素肾病大鼠的肾脏保护作用  

Renoprotective effect and mechanisms of benazepril and pentifylline on adriamycin nephropathy rats

作　　者：杨沿浪[1] 张道友[1] 汪向明[1] 崔明春[1] 吴小东[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》2009年第7期736-740,共5页Chinese Journal of Clinical Pharmacology and Therapeutics

基　　金：皖南医学院中青年教师基金(WK200602AF)

摘　　要：目的:探讨苯那普利、己酮可可碱及两药联合应用对阿霉素肾病大鼠的肾脏保护作用。方法:42只SD大鼠随机取出6只大鼠为正常对照组,余下经尾静脉注射阿霉素制备肾病模型,正常对照组给予等量生理盐水注射。造模成功的大鼠(24 h蛋白尿>100 mg)随机分为模型组、血管紧张素转化酶抑制剂(ACEI)组(苯那普利)、PTX组(己酮可可碱)、联合治疗组(苯那普利加己酮可可碱)。8周后处死大鼠,经腹主动脉取血,检查生化指标;取肾皮质作HE染色,巨噬细胞趋化因子-1(MCP-1)、转化生长因子-β1(TGFβ-1)免疫组织化学染色,应用图像分析系统进行免疫组化半定量分析。结果:联合组与单独用药组比较能有效降低阿霉素肾病大鼠血压[模型组(141±5)mm Hg,PTX组(134±6)mm Hg,ACEI组(130±5)mm Hg,联合治疗组(126±5)mm Hg]。各治疗组均显著降低蛋白尿,ACEI组疗效略优于PTX组,但差别无统计学意义;联合治疗组疗效优于单独治疗组(P<0.01),且可以显著抑制MCP-1、TGFβ-1的表达(P<0.01)。结论:己酮可可碱、苯那普利及两药联用可更好地保护阿霉素肾病大鼠,其机制与其降低尿蛋白、抑制肾脏炎症及抗肾间质纤维化有关。AIM： To investigate the renoprotective effect of benazepril and pentifylline on adriamycin nephropathy rats. METHODS： A total 42 rats were randomly assigned to control group, model group, benazepril treatment group, pentifylline treatment group and combined treatment group. At the 8th week after operation, changes of the 24 hours urinary protein excretion, renal function, TP and Alb were also examined. Immunohistochemistry was performed to investigate renal pathological changes and the expression of MCP-1 and TGF-β1. RESULTS： Combined treatment group could efficiently lowe the blood pressure [ PTX group （134 ± 6） mm Hg, ACEI group（130 ± 5） mm Hg, combined treatment group （126 ± 5） mm Hg, control group（ 141 ± 5） mm Hg] and the contents of proteinuria in treatment groups were decreased, the effect in ACEI group surpassed that in PTX group, but had no significance. The proteinuria in combined group was lowered than in single treatment group （ P 〈 0. 01 ）. Combined treatment group could efficiently decreased the expression of MCP-1 and TGF-β1. CONCLUSION： Benazepril and pentifylline may play a protective role by depressing renal inflammation, interstitial fibrosis and lowering proteinuria. The effect of combination of benazepril and pentifylline is better than that of either.

关 键 词：阿霉素 肾病 苯那普利 己酮可可碱 联合治疗 巨噬细胞趋化因子-1 转化生长因子-Β1 

分 类 号：R965.1[医药卫生—药理学]