洛沙坦和苯那普利早期保肾作用的实验观察  

Experimental observation on the renal protective effects of Losartan and Benazepril during the early phase of disease development

作　　者：胡波[1] 李红叶[2] 杨霁云[3] 丁洁[3] 张敬京[3] 

机构地区：[1]安徽医科大学第一附属医院儿科,100034230022 [2]河南医科大学第一附属医院儿科 [3]北京大学第一医院儿科

出　　处：《中华儿科杂志》2001年第5期296-299,T004,共5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Ⅱ受体 1拮抗剂洛沙坦和血管紧张素转换酶抑制剂苯那普利对肾病大鼠的早期保护作用。方法　 16只大鼠均分 4组 :(1)正常对照组 ;(2 )苯那普利组 ;(3)洛沙坦组 ;(4 )非治疗组。对大鼠单侧肾切除 1周后行阿霉素 (5mg/kg)注射 ,建立动物模型。自手术后分别给予苯那普利 6mg/ (kg·d)或洛沙坦 5mg/ (kg·d)治疗 5周 ,观察大鼠的蛋白尿 ,血总蛋白、白蛋白、肌酐、尿素氮、胆固醇和残余肾组织的病理改变。结果　实验 3周时 ,正常对照组、苯那普利组、洛沙坦组及非治疗组大鼠尿蛋白依次 (下同 )为 2 6 (1 3～ 5 6 )mg/ 2 4h、130 3(10 0 9～ 176 8)mg/ 2 4h、42 7(4 1 9～ 44 2 )mg/ 2 4h和 10 5 8(85 1～ 144 9)mg/ 2 4h (H =11 6 5 ,P <0 0 1)。实验 5周 (结束 )时四组大鼠尿蛋白分别为 4 4(0 7～ 5 8)mg/ 2 4h、5 4 8(32 8～ 72 0 )mg/ 2 4h、2 6 7(2 5 6～ 2 8 1)mg/ 2 4h和43 2 (31 6～ 5 0 9)mg/ 2 4h (H =11 30 ,P <0 0 1) ;血胆固醇分别为 (1 9± 0 3)mmol/L、(5 0± 1 6 )mmol/L、(4 4± 1 4)mmol/L和 (8 7± 2 4)mmol/L (F =11 2 6 ,P <0 0 1) ;肾小球系膜增生率分别为7 3(1 4～ 12 8) %、30 3(8 2～ 6 4 5 ) %、32 8(6 0～ 5 5 0 ) %和 6 5Objective AngiotensinⅡ is thought to be a crucial factor in progressive renal injury. Losartan, an angiotensinⅡ type 1 receptor antagonist (AT1A), selectively inhibits the effect of angiotensinⅡ via AT1 receptor blockade. Benazepril, a new type angiotensin converting enzyme inhibitor (ACEI), fairly well inhibits angiotensin converting enzyme in circulation and tissue. The purpose of this study was to observe the renal protective effects of these 2 agents in rats with nephropathy during the early phase of disease development. Methods All experiments were performed on male 6 month old Sprague Dawley rats weighing about 400 g. Sixteen rats were divided into four groups: normal control rats ( n =4), benazepril treated rats ( n =4), losartan treated rats ( n =4) and non drug treated rats ( n =4). Normal control rats were subjected to sham operation and were injected with normal saline after one week through the tail vein. The rest groups were uninephrectomized and injected adriamycin (5 mg/kg) after one week through the tail vein. Groups Ⅱ or III was treated with benazepril 6 mg/(kg·d) or losartan 5 mg/(kg·d); groups Ⅰ and Ⅳ were allowed to have free access to standard rat chow and tap water for 5 weeks. The protein in urine, serum total protein and albumin, serum creatinine, blood urea nitrogen and serum cholesterol were measured at the 3rd or 5th week, the renal pathological changes of the remnant kidney were investigated at the 5th week when the rats were sacrificed. Results At the 3rd week of the experiment, the protein levels in urine were 2.6(1.3 5.6) mg/24 h, 130.3(100.9 176.8) mg/24 h, 42.7(41 9 44.2) mg/24 h and 105.8(85.1 144.9) mg/24 h ( H =11.65, P <0.01) in normal control, benazepril treated, losartan treated and non drug treated groups, respectively. At the 5th week, the protein levels in urine were 4.4(0.7 5.8) mg/24 h, 54.8(32.8 72.0) mg/24 h, 26.7(25.6 28.1) mg/24 h and 43.2(31.6 50.9) mg/24 h ( H =11.30, P <0.01); the serum cholesterol was

关 键 词：洛沙坦 苯丙氮Zhuo 肾小球硬化症 保肾作用 苯那普利 

分 类 号：R965[医药卫生—药理学]