氯沙坦对幼龄肾硬化大鼠的保护作用及其机制探讨  

Renal protective effects and mechanism of losartan in young rats with glomerulosclerosis

作　　者：胡波[1] 鹿玲[1] 张庆玲[1] 杨霁云[2] 丁洁[2] 张敬京[2] 

机构地区：[1]安徽医科大学第一附属医院儿科,合肥230022 [2]北京大学第一医院儿科,100034

出　　处：《临床儿科杂志》2006年第11期916-919,923,共5页Journal of Clinical Pediatrics

基　　金：安徽省教育厅科研基金(2002kj177zc);CMB基金(93593)资助

摘　　要：目的观察血管紧张素Ⅱ受体-1拮抗体(AT1RA)——氯沙坦对幼龄肾硬化大鼠的保护作用,并探讨其减轻细胞外基质(ECM)积聚的机制。方法17只SD幼龄大鼠(1月龄,体重100g左右)随机分为3组:对照组(5只)、模型组(6只)和治疗组(6只)。对后两组大鼠行单侧肾切除,1周后加阿霉素(5mg/kg)注射,诱导肾硬化模型。术后治疗组予氯沙坦5mg/(kg·d)共12周。观察各组大鼠尿蛋白、血生化指标变化及肾组织的病理改变,并用免疫组化方法检测转化生长因子-β1(TGF-β1)在肾小球的蛋白表达。结果氯沙坦于实验的第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2.41mg/24h,1.97mg/24h,2.96mg/24h,3.54mg/24h比17.28mg/24h,7.39mg/24h,14.20mg/24h,0.55mg/24h(P均<0.01)。实验结束时,氯沙坦形态学上显示有减轻肾小球系膜增生和硬化的作用,治疗组与模型组相比,系膜增生率和硬化指数分别为3.45%、3.36%比35.40%、40.28%和0.25%、0.13%比1.86%、2.61%(P均<0.05);其且下调了TGF-β1在肾小球内的蛋白表达,两组TGF-β1的光密度值(A值)之比为(0.143±0.023)比(0.221±0.036)(P<0.01)。结论在此单侧肾切除阿霉素肾病幼鼠肾硬化模型上,氯沙坦显示了降尿蛋白及减轻肾小球系膜增生和硬化的作用;并提示AT1RA对此肾组织学改变的保护作用可能与下调TGF-β1在肾内的表达以抑制细胞外基质积聚有关。Objectives Clinical and experimental studies indicate that angiotensin Ⅱ （ATⅡ） plays a pathophysiological role in the progression of chronic renal diseases. Angiotensin converting enzyme inhibitor （ACEI） therapy is now widely regarded as a fundamental component of strategies designed to retard the progression of chronic renal diseases. In diabetic patients,ACEI resulted in greater renal protective effects in randomized trials. AT Ⅱ type-1 （AT1） receptor antagonists （RA）,a novel class of renin-angiotensin system inhibitors,inhibit the effects of AT Ⅱ mediated by AT1 receptors, through which they show protective effects predominantly on glomerulosclerosis. Most of these findings came through the studies in adult animals and humans. However,the renal protective effect of AT1 RA has not,so far,been extensively studied in young animals or children and the precise mechanism of this effect remains unclear. The purpose of this study was to observe protective effects of losartan using a model of the focal and segmental glomerulosclerosis in young rats and to find out the mechanism regulating the accumulation of extracellular matrix （ECM）. Methods All experiments were performed on 17 male SD rats （one-month-old,weighing 100 g or so） in three groups： control （n = 5）,model （n = 6） and losartan-treated （n = 6）. Control group were subjected to sham operation and were injected with normal saline after one week via the tail vein. Glomerulosclerosis in young rats was established by means of uninephrectomy and adriamycin （5 mg/kg） administration. After uninephrectomy,losartan-reated group were treated with losartan 5 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 by streptavidin/peroxidase staining. The renal pathological changes of the remnant kid

关 键 词：氯沙坦 肾小球硬化症 局灶性 转化生长因子-β1 幼龄大鼠 

分 类 号：R726.9[医药卫生—儿科]