贝那普利、螺内酯联用对阿霉素肾病大鼠肾小管保护作用的研究

中国临床药理学与治疗学 ›› 2012, Vol. 17 ›› Issue (4): 381-386.

贝那普利、螺内酯联用对阿霉素肾病大鼠肾小管保护作用的研究

杨沿浪^1,2, 邹和群¹, 张道友², 汪裕伟², 李芳霞², 高超清², 徐海红², 陈小妹²

¹南方医科大学附属三院肾内科,广州 510515,广东;
²皖南医学院附属弋矶山医院肾内科,芜湖 241001,安徽

收稿日期:2011-09-20 修回日期:2012-01-21 发布日期:2012-04-28
通讯作者: 邹和群,男,博士,教授,博士生导师,研究方向:肾小管间质肾病学、食物过敏原相关IgA肾病发病机制及其诊断治疗。Tel: 13602825868 E-mail: hequnzou@hotmail.com
作者简介:杨沿浪,男,在读博士,主治医师,研究方向:慢性肾小球疾病。Tel: 13855366863 E-mail: yangyanlang@126.com
基金资助:
安徽省高校省级自然科学研究项目(KJ20011Z384);2009年皖南医学院中青年科研基金项目(WK200933F)

Renal tubular protection effect of combining benazepril and spironolactone in adriamycin-induced nephritic rats

YANG Yan-lang^1,2, ZOU He-qun¹, ZHANG Dao-you², WANG Yu-wei², LI Fan-xia², GAO Chao-qing², XU Hai-hong², CHENG Xiao-mei²

¹Department of Nephrology, Nanfang Medical University Affiliated 3th Hospital, Guanzhou 510515, Guandong, China;
²Department of Nephrology, Wannan Medical College Affiliated Yijishan Hospital, Wuhu 241001, Anhui, China

Received:2011-09-20 Revised:2012-01-21 Published:2012-04-28

摘要/Abstract

摘要： 目的: 观察贝那普利、螺内酯联合应用于阿霉素肾病大鼠降低蛋白尿及增加的肾小管保护作用。方法: 42只SD大鼠随机抽取7只为正常对照组,余下经尾静脉注射阿霉素制备肾病模型。6周后29只造模成功的大鼠(24 h 尿蛋白>100 mg)随机分为:模型组(n=7),贝那普利组(n=8),螺内酯组(n=7),贝那普利和螺内酯联合治疗组(联合用药组,n=7)。分别于6、12、18周末收集 24 h 尿液,检测 24 h 尿蛋白,并于18周末测尿视黄醛结合蛋白(RBP)后,处死大鼠经腹主动脉取血液标本检测生化指标。取出肾组织HE染色,并采用免疫组织化学方法检测肾小管间质转化生长因子-β₁(TGF-β₁)的表达。结果: 各治疗组均能显著降低阿霉素肾病大鼠血压、蛋白尿,升高血清白蛋白(P<0.05),其中贝那普利组和联合治疗组疗效优于螺内酯组,以联合治疗组疗效最为显著;与模型组比较各治疗组尿RBP水平均下降(P< 0.01),其中联合治疗组疗效优于单独治疗组(P< 0.01)。联合治疗组抑制TGF-β₁的表达优于治疗组和模型组。治疗组尿RBP和TGF-β₁均表现为强相关(r=0.735、r=0.845、r=0.585)。结论: 在阿霉素大鼠模型中,贝那普利和螺内酯联合应用能降低蛋白尿,抑制TGF-β₁合成,减轻肾小管损伤。

关键词: 阿霉素肾病, 大鼠, 贝那普利, 螺内酯, 蛋白尿, 尿视黄醛结合蛋白, 转化生长因子-β₁

Abstract: AIM: To investigate the renal tubular protection effect of combining benazepril and spironolactone in adriamycin-induced nephritic rats. METHODS: Male Sprague-Dawley(SD) rats were randomly separated to control group, model group, benazepril treatment group, spironolactone treatment group and combined treatment group. At the 6^th,12^th,18^th week, 24 hours urinary protein excretion were examined, meanwhile after 18th week the rats were executed, biochemical indicators and urinary retinene binding-protein(uRBP) were detected. Immunohistochemistry was performing to investigate renal pathological change and the expression of TGF-β₁. RESULTS: Contrast to model group, solo treatment groups and combined treatment group could efficiently lowered the blood pressure, proteinuria and increased serum-albumin(P<0.05), meanwhile, the combined group have most significant effect. Treatment groups could reduce the levels of uRBP excretion (P<0.01), the level of it in the combined group is lower than those of individual treamtment groups (P<0.01). The combined group could efficiently decrease the expression of TGF-β₁(P< 0.01). In the treatment groups, urinary RBP and TGF-β₁ was correlated significantly (r=0.735,r=0.845,r=0.585). CONCLUSION: In the adriamycin-induced nephropathic rats, combination of benazepril and spironolacton may decrease efficiently the content of protinuria, the level of uRBP and blood pressure, decrease the expression of TGF-β₁ in renal interstitial, arrest the progress of renal tubular injury.

Key words: Adriamycin-induced nephritic, rat, Benazepril, Spironolactone, Proteinuria, Urinary retinene binding-protein, Transforming growth factor-β₁

中图分类号:

R692.6

杨沿浪, 邹和群, 张道友, 汪裕伟, 李芳霞, 高超清, 徐海红, 陈小妹. 贝那普利、螺内酯联用对阿霉素肾病大鼠肾小管保护作用的研究[J]. 中国临床药理学与治疗学, 2012, 17(4): 381-386.

YANG Yan-lang^1,2, ZOU He-qun¹, ZHANG Dao-you², WANG Yu-wei², LI Fan-xia², GAO Chao-qing², XU Hai-hong², CHENG Xiao-mei². Renal tubular protection effect of combining benazepril and spironolactone in adriamycin-induced nephritic rats[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2012, 17(4): 381-386.

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