苯那普利对幼鼠的保肾作用及其部分机制探讨  

Experimental study of the renal protective effects and mechanism of benazepril in young rats with glomerular sclerosis

作　　者：胡波[1] 李红叶[1] 杨霁云[1] 丁洁[1] 张敬京[1] 

机构地区：[1]北京大学第一医院儿科

出　　处：《中华儿科杂志》2002年第5期288-291,共4页Chinese Journal of Pediatrics

基　　金：CMB基金资助项目 (93 5 93 )

摘　　要：目的　观察血管紧张素转换酶抑制剂 (ACEI)———苯那普利对幼龄肾硬化大鼠的保护作用 ,并探讨其调节肾小球细胞外基质 (ECM)积聚的作用机制。方法　将 16只SD幼龄大鼠 (1个月龄 ,体重 10 0g左右 )分为 3组 :(1)正常对照组 (5只 ) ;(2 )模型组 (6只 ) ;(3)治疗组 (5只 )。对大鼠行单侧肾切除 1周后加阿霉素 (5mg/kg)注射建立肾硬化模型 ,术后即对治疗组给予苯那普利 6mg/(kg·d) ,共 12周 ,观察大鼠尿蛋白 ,肾功能等血生化指标和残余肾组织的病理改变以及用免疫组化的方法检测转化生长因子 β1(TGF β1)在肾内的表达。 结果　苯那普利于治疗的第 7、9、12周显示出较好的降尿蛋白作用 ,治疗组尿蛋白与同期模型组相比分别为 5 3(3 9～ 13 4 )mg/2 4h比 13 9(12 4～17 6 )mg/2 4h(P <0 0 5 )、1 8(0 3～ 3 6 )mg/2 4h比 17 3(8 7～ 31 7)mg/2 4h (P <0 0 1)、5 9(1 3～8 3)mg/2 4h比 14 2 (10 9～ 2 3 8)mg/2 4h (P <0 0 1) ;形态学上显示有减轻系膜增生和硬化的作用 ,与模型组相比系膜增生率和硬化指数分别为 8 0 (5 0～ 13 1) %比 35 4 (11 0～ 6 7 5 ) % ,0 3(0 3～ 0 9)比 1 9(0 3～ 6 7) (P均 <0 0 5 ) ;并降低了TGF β1在肾内的蛋白表达 (PObjective Angiotensin Ⅱ is thought to be a crucial factor in the progressive renal injury Benazepril, a new type angiotensin converting enzyme inhibitor (ACEI), fairly well inhibits the angiotensin Ⅱ activity by inhibiting the angiotensin converting enzyme in the circulation and tissues, and shows a protective effect on glomerulosclerosis Those kind of the studies mostly were carried out in adult animals and humans However, the renal protective effect of ACEI has not, thus far, been extensively studied in fawn hooded and childhood The purpose of this study was to observe protective effect of benazepril in a young rat model with glomerulosclerosis and to analyze the mechanism of benazepril regulating the production and degradation of extracellular matrix (ECM).Methods All experiments were performed on male SD rats (one month old, weighing around 100 g) Sixteen rats were divided into three groups: normal control rats ( n =5), model rats ( n =6) and benazepril treated rats ( n =5) Normal control rats were subjected to sham operation and, after one week injected with normal saline via the tail vein Animal model with glomerulosclerosis was established by uninephrectomy and adriamycin (5 mg/kg) injection in the rest groups After uninephrectomy, benazepril treated rats were administrated with benazepril 6 mg/(kg·d) for 12 weeks The levels of urinary protein excretion, serum total protein, albumin, serum creatinine, blood urea nitrogen and total cholesterol were measured at regular intervals The expression of transforming growth factor β1 (TGF β1) in the glomeruli was detected with the immunohistochemical method The renal pathological changes of the remnant kidney were investigated at the end of the experiment Results Compared to model group, benazepril showed effect on reducing the proteinuria at the 7th, 9th and 12th week The urinary protein excretions were 5 3 (3 9-13 4) mg/24 h vs 13 9 (12 4-17 6) mg/24 h ( P <0 05), 1 8 (0 3-3 6) mg/24 h vs 17 3 (

关 键 词：苯丙氮卓类 血管紧张素转换酶抑制药 肾小球硬化症 细胞外基质 转化生长因子Β 动物实验 苯那普利 保肾作用 

分 类 号：R965[医药卫生—药理学]